TWI359638B - Microbicidal composition - Google Patents

Abstract

Synergistic microbicidal compositions containing N-(n-butyl)-1,2-benzisothiazolin-3-one or N-methyl-1,2-benzisothiazolin-3-one.

Description

1359638 IX. Description of the Invention: [Technical Field to Which the Invention Is Applicable] The present invention has a side effect of selecting (four) _blnation, which has higher activity than that observed for individual antibacterial agents. [Prior Art] Commercially available antibacterial agents do not provide effective control of microorganisms, even at high use concentrations, due to resistance to certain types of turtle microorganisms (eg 'these are against certain antimicrobial agents' Resistant () resistant), or due to invasive environmental conditions. Combinations of different antimicrobial agents are sometimes used to provide comprehensive microbial control for a specific purpose use environment. For example, U.S. Patent Application Publication No. 4/4/14,799 discloses an N-(n-butyl)-L2-benzisothiazolin-3-enone (ΒΒιτ) and 2-methyl-isothiazoline- The synergistic combination of 3-ketone (ΜΙ) is limited to a ratio of ΒΒιτ to μι of 10 ·· 1 to 丨·6?:1. However, there is still a need for additional combinations of antimicrobial agents that have enhanced activity against various strains of microorganisms to provide effective control of microorganisms. Furthermore, for environmental and economic benefits, it is desirable to include a combination of lower concentrations of individual antimicrobial agents. The present invention provides an additional combination of such antimicrobial agents to solve this problem. SUMMARY OF THE INVENTION The present invention is directed to an antibacterial composition comprising: (a) N_(n-butyl)-1,2-benzisothiazolin-3-enone; and hydrazine) at least one antibacterial agent, Selected from the group consisting of benzaik〇nium chloride, benzethonium chloride, benzyl alcohol, benzisothiazolone, 2-bromo-2-nitropropanediol, Glycol, octyl diol (capryly) [ 5 93646

1359638 - Lu 1>^〇1), chlorobenzene scales ((: 111〇印1^1^5111), 1,3-dihydroxymethyl-5,5-dimercaptoinourone, disulfide Base-2,2'-bis(N-mercaptobenzamide), ethylenediaminetetraacetic acid or its salt, ethyl p-hydroxybenzoate, hexamidinediisethionate, double Hexetidine, methyl benzoate, phenoxyethanol, linoleamidopropyl PG-dimonium chloride phosphate, coconut oil guanamine Cocamidopropyl PG-dimonium chloride phosphate, propyl benzoic acid propylate, sorbic acid or its salt, 1-(3-chloroallyl)-3,5, 7-Triaza-1-azaindene adamantane chloride, dehydroacetic acid or a salt thereof, benzoic acid or a salt thereof, and citric acid or a salt thereof. The present invention is directed to an antibacterial composition comprising: (a) N-methyl-1,2-benzisothiazolin-3-one; and (b) at least one antibacterial agent selected from N-(n-butyl)-1,2-benzisothiazoline -3-ketone, benzyl chloride, ammonium benzyl chloride (benzethoniu) m chloride), benzoquinone, benzopyrene 0 ketone, ketone, 2-bromo-2-nitropropane-1,3-diol, butanediol, octanyl diol, chlorpheniramine, Dithio-2,2'-bis(N-methylbenzoguanamine), ethylenediaminetetraacetic acid or its salt, ethyl p-hydroxybenzoate, hexamethylene dihydroxyethyl sulfonate, dioctane Hexetidine, decyl hydroxybenzoate, phenoxyethyl, linoleamidopropyl PG-dimonium chloride phosphate, coconut oil decylamine Propyl propylene glycol-cobalidopropyl PG-dimonium chloride phosphate, sorbic acid or its salt, p-benzoic acid, 1-(3-chloroallyl)-3,5, 7-triaza-1-nitrogen adamantane chloride, dehydroacetic acid or 6 93646 1359638 I » /, succinic acid or its salt, citric acid or its salt, and n-zinc pyrithione [Embodiment] "BBIT'1 N_(n-butyl)-1,2-benzisothiazolin-3-ylindole."ΕΓ)ΤΔ,,ν, is ethylenediaminetetraacetic acid. ΜΒΙΤ,,Ν,曱基-^2-Benzoisoindole-3-_. As used herein, unless otherwise stated in the text, the following terms - have the specified definition. Terminology, antibacterial agent , means a compound that kills at the location, kills, inhibits, or controls the growth of microorganisms; the antibacterial agent contains an antibacterial, antifungal, and antialgatic agent. The term, microorganism, includes, For example, fungi (eg, yeasts and molds), bacteria, and algae. The term, at position t〇CUS) means an industrial system or product that is susceptible to microbial contamination. The following abbreviations are used throughout this specification: 卯m = parts per million by weight (reset / heavy) 'mL = home rise' ATCC = US strain center, mbc = minimum biocidal concentration ), and • MK> minimum inhibitory concentration. Unless otherwise indicated, the temperature is in degrees Celsius = rc) and the percentage relationship (%) is by weight. The organic antibacterial agent is given in ppm (weight/weight) based on the active ingredient. The compositions of the present invention are unexpectedly found to have an enhanced antibacterial effect at a concentration of the combined active ingredient below the concentration of the individual antimicrobial agent. In the specific embodiment of the present invention, the antibacterial composition containing the toothed 3·iso(4) is relatively low in concentration, preferably not more than 1000 ppm, more preferably not more than 500 ppm, more preferably not exceeding! 〇〇ppm, and the best does not exceed. The concentration of W匕3-iso(tetra)linone in the silk of the present invention is based on the activity of the composition 93646 7 1359638, the total weight of the ingredients, that is, does not contain any solvent, carrier, agent, stabilizer or other possible - and static ~ "one quality elixirs. In the present invention ''antimicrobial' composition contains less qing, if it is not more than ppm, better not more than and less than 5 〇 Ppm 5_氯·2_methyl_4_iso. 嗟 琳 _ _3, and in one embodiment of the invention, the antibacterial composition comprises • n-butyl)-1,2-stupid (4) Lin _3_ ketone and gasified phthalic acid recorded. Compared with N 曰 (n-butyl h, 2 benzoisoindole _3 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ The ratio is from 1: (U to 1:3 〇, more preferably from 1-3 to U. In one embodiment of the invention, the antimicrobial composition comprises N-(n-butyl) 4, benzo Isothiazoline _3-ketone and benzylammonium chloride. The weight ratio of preferred (n-butyl)-1,2-benzisothiazoline _3-ketone to benzylammonium chloride is from 1: More preferably, from 0.02 to 1:15', from 1:1 to 1. In the embodiment of the present invention, the antibacterial The composition comprises N (n-butyl) hydrazine, 2 - benzoisothiazoline -3- ketone and benzyl alcohol. Preferably, N (n-butyl benzisothiazoline -3- ketone to benzyl alcohol) The weight ratio is from 1:1 to 1:1000, more preferably from 1:2 to 1:8, more preferably from 1:3 to 1:800. In one embodiment of the invention, the antimicrobial The composition comprises N (n-butyl)-L2-benzisothiazolinone and anthracene, 2_stupothithiathiazolinium. Preferably 'N_(n-butyl)+2-benzisoindole The weight ratio of saliva to winter benzoisothiazoline-3-one is from 1:0.02 to 1:20, more preferably from 1:0.02 to 1:16. In one embodiment of the invention, the antibacterial The composition comprises 8 93646 1^59638 N_(n-butyl)· 1,2- benzoisothiazolidine and 2·di·2_nitropropanone•1:3-diol. Preferably , N•(正·butyl H,2•Benzene isoindole (5) with the pair 2 / odor 2- determinate propyl _1, 3 diol weight ratio is self-sufficiency: 〇.〇1 to 1 In one embodiment of the invention, the antimicrobial composition comprises N-(n-butyl)-1,2-p-isoisothiazoline-3-one and butanediol. Preferably, N- (n-butyl η, benzo The weight ratio of isothiazolinone to butanediol is from 1 to 1:5000, more preferably from 1:3 to 1:5. In one embodiment of the invention, the antimicrobial composition comprises ruthenium. (n-butyl)-1,2-benzisothiazoline-3-one and octanediol. Preferably, Ν(n-butyl)-l,2-benzisothiazoline_3_ The weight ratio of the ketone to the octyl diol is from 1.1 to 1:1000', more preferably from 1:3 to 1:1. In one embodiment of the invention, the antimicrobial composition comprises ruthenium (n-butyl)-1,2-benzisothiazoline-3-one and chlorobenzene. Preferably, the weight ratio of Ν(n-butyl)_1,2-benzisothiazoline_3-keto-p-chlorobenzoate is from 1:0.5 to 1:700, more preferably from 1:1 to 1:5〇〇. In one embodiment of the invention, the antimicrobial composition comprises Ν-(n-butyl)_ι, 2-benzisothiazolin-3-enone and 〗 〖3-Dihydroxymethyl _5,5_ Methyl carbendazim. Preferably, the weight ratio of Ν_(n-butyl)benzisothiazoline_3_ ah to ι,3·di-methyl-5,5-dimethylhydantoin is from 1: 〇. 〇2 to 1:200' Better from 〇6 to ι:ΐ6〇. In one embodiment of the present invention, the antimicrobial composition comprises (n-butyl)-1,2-benzisothiazoline-3-enone and disulfo-2,2,_bis (Ν_ fluorenyl) Benzoylamine), preferably, Ν _ (n-butyl)_ j,2 _benzisothiazoline·3 ketone-dithio- 2,2'-bis(Ν-methylphenylhydrazine) The weight ratio of indoleamine is from 1: 9 93646 1359638 • 0.02 to 1:160. In one embodiment of the present invention, the antibacterial composition comprises N-(n-butyl)-I, 2, streptoisothiazoline-3-enone and EDta or a salt thereof, preferably EDTA. Preferably, the weight ratio of Ν·(n-butyl V1,2•benzisothiazoline_3_酉 to EDTA or a salt thereof is from u to k5〇〇, more preferably from ι:3 to 1 : 500. In one embodiment of the present invention, the antibacterial composition comprises .N-(n-butyl)_1,2-benzisothiazolin-3-enone and ethyl p-hydroxybenzoate. Preferably, the weight ratio of 'N-(n-butyl)-oxime, 2·benzisothiazoline_3_one to p-hydroxybenzoic acid ethyl vinegar is from 1:1 to 1:200, more preferably from 1:2 to 1:2. In one embodiment of the present invention, the antimicrobial composition comprises N-(n-butyl)-1,2-benzisothiazoline-3-one and hexanone. Dihydroxyethyl sulfonate. Preferably, the weight ratio of N-(n-butylbenzisothiazoline-3-one to hexamethylene diethylate is from 1:2 to 1 : 3. In one embodiment of the invention, the antimicrobial composition comprises Lu N-(n-butyl)-1,2-benzisothiazolin-3-one and dioctylhydropyridine. Preferably, The weight ratio of N-(n-butyl)-1,2-benzisothiazoline-3-one to dioctylhydropyridine is from 1:0.02 to 1:40. In one embodiment of the present invention, Antibacterial group Containing (n-butyl)-1,2-benzisothiazoline-3-ol and methyl p-hydroxybenzoate. Preferably 'N-(n-butyl)-1,2-benzo The weight ratio of the isothiazoline -3- ketone to the oxime hydroxybenzoate is from 1:0.2 to 1:250, more preferably from i:0.5 to 1:240. In one embodiment of the invention, this The antibacterial composition comprises N-(n-butyl)-1,2-benzisothiazolin-3-enone and phenoxyethanol. Preferably 10 93646 1359638 'N-(n-butyl)-1 The weight ratio of 2·benzisothiazolin-3-one to phenoxyethanol is from 1:0.5 to ι:8〇〇, more preferably from ι:ι to ι:8〇〇. In one embodiment, the antimicrobial composition comprises Ν-(n-butyl)-1,2- benzoisothiazolin-3-enone and linseed guanidinium propyl propylene glycol-diammonium chloride Preferably, the weight ratio of Ν-(n-butyl)-1,2-benzisothiazolin-3-one to linseed oil allylpropyl propylene glycol _ gasified dimethyl ammonium phosphate vinegar is 1:8 to 1:500. In one embodiment of the present invention, 'this antibacterial composition comprises hydrazine (butyl) I']-benzin 嗔 嗔 琳 ] ] ketone and ketone oil Diol decyl ammonium phosphate phthalate. Preferably, Ν-(n-butyl)-1,2-benzisothiazolin-3-one to coconut oil decyl propyl propylene glycol _ gasified bismuth The weight ratio of the ammonium citrate is from 1:1 to 1:4. In one embodiment of the invention, the antimicrobial composition comprises N-(n-butyl)-1,2-benzene. And isothiazoline _3 ketone and propyl paraben. Preferably N (n-butyl)_ι, 2 benzoisoindole _3 ketone versus p-hydroxybenzoic acid propyl φ The weight ratio is from 1:1 to 1:5〇〇, more preferably from 1:4 to 1:4〇〇. In a specific embodiment of the present invention, the antibacterial composition comprises hydrazine (n-butyl)_ι, 2-benzisothiazolidine-3-ol and sorbic acid or a salt thereof, which is preferably sorbed with sorbic acid. Preferably, Ν_(positive-butyl hydrazine, 2 benzophenanthrene. The weight ratio of sorrel _3_ ketone to sorbic acid or its salt is from 1:6 to 1:12 〇〇. In a specific example, the antimicrobial composition comprises n-butyl)-1,2-benzisothiazolinone and 丨_(3_availyl)-3,5,7-triaza rust adamantane Vapor. Preferably, n-butyl fluorene, 2-benzoiso(tetra)lin-3-lysine 3' chloropropyl)-3,5,7·triaza 93464 11 1359638 -1-azaindene adamantane chloride The weight ratio is from 1:0.5 to 1:2, more preferably from 1:1 to 1:200. In a specific embodiment of the present invention, the antibacterial composition comprises N (n-butyl hydrazine--benzopyranyl _3-ketone and degassed acetic acid or a salt thereof, preferably sodium dehydroacetate). Preferably, the weight ratio of Ν_(n-butyl hydrazine, 2_benzoxanthion-3-one to dehydroacetic acid or a salt thereof is from 1:5 to 1:7, more preferably from 1:0.7 to 1:5 〇' In one embodiment of the present invention, the antibacterial composition comprises Ν-(n-butyl)benzisothiazolin-3-enone and benzoic acid or a salt thereof, and benzene Sodium formate is preferred. Preferably, the weight ratio of N_(n-butyl, stupid isothiazoline-3-enoate to benzoic acid or its salt is from 1:1 to U, more preferably from 1:13. To l: i600. In the specific embodiment of the present invention, the antibacterial composition comprises = (n-butyl benzisothiazoline _3 ketone and citric acid or a salt thereof, to 柊 cylinder: car Preferably, the weight ratio of N•(n-butyl)-1,2-benzisothiazolin-3-one to lemon tart or its salt is from 1:5 〇 to the present invention-specific In an example, the antibacterial composition comprises a group of methyl-1,2·benziso(tetra)line_3_one and ν_(n-butyl)#benzo Preferably, Ν 曱 丨 丨, benzoisothiazoline _3 ketone butyl butyl)-1,2-benzisothiazoline _3 ketone The weight ratio is from 丨.〇 to 1:30, more preferably from 1:0.5 to 1:24. In one embodiment of the invention, the antimicrobial composition comprises, the iso-isothiazoline-3-one The ratio of the weight of the chlorodimethylammonium chloride to 93646 12 1359638 is from 1:1 to 1:20, more preferably from 1:0.2 to 1:20. In one embodiment of the invention, the antibacterial property The composition comprises Ν-methyl-1,2-p-isothiazoline-3-enone and gasified benzylammonium sulphate. Preferably, ν_methyl·1,2-benzisothiazoline _3-ketone The weight ratio of the gasified benzalkonium chloride is from 1:0.3 to 1:0.6', more preferably from 1:4 to 1:6. In one embodiment of the invention, the antimicrobial composition comprises hydrazine. -Methyl-1,2-benzisothiazoline-3-ol and benzofuran. Preferably, Ν-mercapto•-1,2-p-isoisothiazoline_3-keto-p-nonyl alcohol The weight ratio is from 1: 丨 to • 'better from 1:5 to 1:8 〇〇. In one embodiment of the invention 'this antimicrobial composition comprises Ν-methyl-1,2-benzo Isothiazole _3_ ketone and benzisothiazolinone. Preferably, Ν-mercapto-1,2·benzopyranin singer·3__p-benzopyrene. The weight ratio of seletonone is from 1:0.1 More preferably, it is from 1:25 to 1:2. In the embodiment of the present invention, the antibacterial composition comprises Ν_methyl 1,2-benzisoindole-3__ And 2_ desert_2_nitropropanediol. Preferably, N_mercapto-1,2-benzisoxazole _3_one to 2_bromo_2_nitropropane _1,3_ The weight ratio of the diol is from 1:0.1 to 1:1 Torr. In a specific embodiment of the invention, the antimicrobial composition comprises N-mercapto-1,2-benzisoindole _3_ 酉 and butane diol. Preferably, the weight ratio of n-methyl-1,2-benzisothiazoline_3__ to butanediol is from I" to 1:400, more preferably from 1:13 to 1:375. In one embodiment of the present invention, the antibacterial composition comprises N-methyl-1,2·benzindole and octanediol. Preferably, Ν·methyl-1,2-benzo-isosine (d) is heavier to octanediol [Μ to 13 93646 1359638 ' 1:1500. In one embodiment of the invention, the antimicrobial composition comprises N-mercapto-1,2-benzisothiazoline-3-one and chlorophenylglycol. Preferably, the weight ratio of N-methyl 1,2-benzisoindole _3-keto-p-chlorobenzoate is from u to 250 °', preferably from 1:5 to 1:250. In one embodiment of the invention, the antimicrobial composition comprises N-methyl-1,2-benzisothiazolin-3-one and disulfo-2,2,-bis(N-methylbenzene) A brewing amine). Preferably, the weight ratio of 'N-methyl-hydrazine, 2_benzisothiazolinone to disulfoyl 2'2-bis(N-methylbenzoate) is from 1:1 to 1:1. In one embodiment of the present invention, the antibacterial composition comprises N-methyl-1,2-benzisothiazoline-3-enone and EDTA or a salt thereof, preferably EDTA. Preferably, N-mercapto], 2_benzisothiazolidine-3-one is heavy on EDTA or a salt thereof! The ratio is from 1::! to 1:4〇〇, preferably from 1:1〇 to 1:32〇. In one embodiment of the invention, the antimicrobial composition comprises N-methyl-1,2-benzisothiazolin-3-one and ethyl p-hydroxybenzoate. Preferably, the weight ratio of Ν-mercapto-1,2-benzisothiazoline-3-one to ethyl p-hydroxybenzoate is from 1.5 to 1:500, more preferably from 1:7 to 1:_. In a specific embodiment of the invention, the antimicrobial composition comprises fluorenyl 1,2-benzisothiazolin-3-enone and hexamethylene dihydroxyethyl sulfonate. Preferably, 'Ν-methyl_ι,2-benzoxanthene _3, the ratio of the weight I of the hexanoate ethyl hexanoate is from 1:0.1 to 1:5, more preferably from 1:〇" to 1:3. In a specific embodiment of the invention, the antimicrobial composition comprises sulfhydryl-1,2-benzisoindole. Sitting on the _3_ ketone and double xin hydrogen bite. Preferably, the weight ratio of ν_mercapto-1,2-benzisothiazolinone to dioctylhydrogenidine is from ι:〇 ι to 14 93646 kiss 38 1:40. In one embodiment of the invention, the antimicrobial composition comprises N-methyl-1,2-benzisoindole. Sitting on the _3__ and cumene p-hydroxybenzoate. Preferably, the weight ratio of the indolyl-1,2-benzoisosinyl-3-ketone to the paraformic formic acid methyl vinegar is from 1:1 to 1:400, more preferably from 1:2 to 1. :4〇〇. In one embodiment of the invention, the antimicrobial composition comprises N-methyl-1,2-benzisoindole yttrium and phenoxyethanol. Preferably, the weight ratio of methyl-1,2·benzoindole/3__p-phenoxyethanol is from 1:120 to 1:160. In one embodiment of the invention, the antimicrobial composition comprises Ν_methyl-1,2-benzisothiazolin-3-enone and linseed amidoxime propylene glycol-vaporized decyl ammonium phosphate. Preferably, the weight ratio of Ν_methyl-hydrazine, 2_benzisothiazoline _3 ketone to linseed guanidinium propyl propylene glycol _ gasified dimercaptolide is from 1:3 to 1: 400. In one embodiment of the present invention, the antibacterial composition comprises Ν_lu methyl-1,2-benzisothiazolin-3-one and coconut oil decyl propyl propylene glycol-dimethylammonium chloride chlorate . Preferably, the weight ratio of Ν_mercaptobenzisisothiazoline_3_ _ to coconut oil guanidinium propyl propylene glycol _ gasified dimercapto ruthenium ester is from 1:0 to 1:25, most Jia is from 1:4 to 1:125. In a specific embodiment of the present invention, the antibacterial composition comprises Ν_mercapto-1,2-p-isoisothiazoline-3-one and sorbic acid or a salt thereof, preferably potassium sorbate. Preferably, the weight ratio of Ν-methyl-1,2-benzisothiazoline-3-one to sorbic acid or a salt thereof is from 1:5 to ι:6〇〇, more preferably from 1:8. Until 1:6. In one embodiment of the invention, the antimicrobial composition comprises Ν 15 93646 1359638 - subunit_1, 2-benzisothiazolin-3-one and propyl paraben. Preferably, the weight ratio of N-methyl-1,2-benzisothiazoline-3-one to propyl p-hydroxybenzoate is from 1:10 to 1:1200, more preferably from 1:13. To 1:1200. In one embodiment of the present invention, the antibacterial composition comprises Ν_methyl-1,2-benzisothiazoline _3-one and cis-indene chlorinated propyl)_3,5,7_3 Aza-1 -nitrogen adamantane chloride. Preferably, Ν_曱基_〗, 2_benzisothiazepine-3, for cis-s(3_a-allyl)_3,5,7-triaza-nitrodiazepine acetyl alkane The weight ratio is from 1:2 to 1:4, more preferably from 1:3 to 1:200. In one embodiment of the present invention, the antibacterial composition comprises Ν_methyl-1,2-benzisothiazoline-3-one and dehydroacetic acid or a salt thereof, preferably sodium dehydroacetate. Preferably, the weight ratio of Ν_曱yl ν1,2-benzisothiazoline-3-one to dehydroacetic acid or a salt thereof is from 1:1 to 1:5. In one embodiment of the present invention, the antibacterial composition comprises: mercapto-1,2-p-isoisothiazoline-3-enone and benzoic acid or a salt thereof, and sodium benzoate is further preferred. Preferably, the weight ratio of fluorenyl-mercapto], 2_benzisothiazoline-3-one to succinic acid or a salt thereof is from 1:1 to 1: _, more preferably from 1:4 to 1 :6〇(八) In the specific embodiment of the present invention, the antibacterial composition comprises I decyl-1,2-benzisoindole _3-ketone and citric acid or a salt thereof, in the form of a rod-like acid Preferably. Preferably, the weight ratio of Ν-methyl 笨 并 嗟 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ . In a specific embodiment of the invention, the antimicrobial composition comprises sulfhydryl-1,2-benzisoindole. Sit with m and bite the sulphur. Preferably, ν· 93646 16 1359638 f-p-isoisothiazoline _3, p. The ratio of pyridine sulfur is from 1:0.01 to 1:6, more preferably from 1:04 to 1:4. The antibacterial agent in the composition of the present invention can be used "by itself," or can be used in combination with a solvent or a solid carrier. Suitable solvents include, for example, propanol, water, diol, Such as ethylene glycol, propylene glycol, diethylene glycol, ethylene glycol and polypropylene glycol; glycols; alcohols such as decyl alcohol, ethanol, propanol, phenylethyl alcohol and phenoxypropanol " the same, such as C, and Methyl ethyl ketone; vinegar, such as ethyl acetate, butyl acetate, 耱 舻 r r 駄 駄 及 及 及 及 及 ; ; ; ; ; ; ; ; ; ; 酉 酉 酉 酉 酉 酉 酉 酉 酉 酉 酉 酉 酉A mixture of the above solvents. Preferably, the solvent is selected from the group consisting of water, glycol, diol hydrazine, vinegar, and a mixture of various solvents. Suitable solid carriers include, for example, cyclodextrin, oxidized m Soil, earthworms, cellulosic materials, gold and alkaline earth (eg, sodium, potassium, potassium) metal salts (eg, chlorides, nitrates, deserts, sulfates) and charcoal. When antibacterial ingredients are formulated in solvents This formulation may optionally contain a surfactant. When the formulation contains interfacial activity, The S is usually an emulsive C〇ncentrates, an emulsion, a microemulsive concentrate, or a microemulsion. The emulsion concentrate forms an emulsion immediately after adding a sufficient amount of water. Microemulsions are formed immediately after the addition of sufficient water. Such emulsified concentrates or microemulsified concentrates are generally known in the art; such formulations preferably do not contain a surfactant. U.S. Patent No. 5,444,078 Refer to the general and specific details of further preparation of various microemulsions and microemulsified concentrates. Only a few knives can be formulated into a dispersion form. The solvent of the dispersion is 93646 17:: for cutting or water, preferably with water. These dispersions may contain adjuvants, coloring agents: color, pigment I--) A thickener, anti-lingering agent, dispersing agent 'filling pigment, surfactant, biodispersant, sulfosuccinate Salt, %%, furanone's 僧 — — 加 加 加 加 % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % % Coolant can be used to mix The solvent of a commercially available antibacterial agent is the same or different. However, for most antibiotic agents, the water system is preferred. Preferably, the two solvents are miscible. It should be understood that the antibacterial component of the present invention may be added to the position at the same time or at the same time, or may be combined before being added to the position. Preferably, the second antibacterial agent of the first antibacterial agent is added to the position with the same or When the antibacterial agents are added simultaneously or sequentially, the individual jobs may each contain an adjuvant, such as, for example, a solvent, a sputum agent, an anti-image agent, a colorant, a chelating agent (such as ethylenediaminetetraacetic acid, B: amine di-broken (2) acid, imine succinate, its salt), dispersant, surfactant, biodispersant, sulfosuccinate, box, ketone, multivalent cation, stability Agent, scale inhibitor and anti-corrosion rice additive. The antibacterial composition of the present invention can be used to inhibit microorganisms or higher aquatic organisms (such as protozoa, by introducing an antibacterial effective amount of the composition above, inside, or at the location where the microorganism is attacked. Growth of invertebrates, bryozoans, dinoflagellates, crustaceans, mollusks, etc. Suitable locations include 'for example: industrial water; electrocoat deposition system; cooling tower; air cleaner; 18 93646 1359638 gas scrubber; mine crossing; waste Yuxu persimmon. #广果,水水处理, Decorative fountain; reverse osmosis filtration; more than 遽 (5) trafiItration); 虔 carrier water; evaporative condenser · heat exchanger; pulp and paper solution and additives; temple powder; plastic; emulsion; dispersant; pigment, juice, paint, Such as varnish; architectural products, such as 朦 sticky cement, caulking paste and sealant; construction adhesives, such as Tao Jing adhesive, carpet backing adhesive sheet! and double-bond adhesive 'industrial or consumer adhesive; photography Chemicals; printing liquids; household items such as bathroom and kitchen cleaning products; beauty products; = products: shampoo; fat; detergent; industrial cleaners; floor light u Lin laundry room silk water; metal processing liquid; Conveyor belt lubricating fluid; liquid fluid (hydraulicfluid), · leather and leather products; textiles, textile products 'wood and wood products, such as plywood, wood chips (also coffee _, wall Plate, chipboard (eboard), laminated beam, oriented granule plate, hard plate and pull plate, petroleum refining liquid; fuel; oil field liquid, such as injection gap liquid and drilling mud; agricultural adjuvant preservation; interface Preservation of active agents; medical =; diagnostic test, food preservation, such as plastic or paper food capsules: pasteurizer for the second industry process; toilet, recreational water; pond; and mineral spring. Preferably, the antibacterial composition of the present invention is used to inhibit the growth of microorganisms at the location of the selected or the genus: (4) liquid and Tianli Yidian powder; emulsion; dispersant; pigment; milk = table glue, Such as ceramic a binder, carpet backing and products; printing liquid; household items, such as bathroom and kitchen cleaning: supplies; cosmetics, · shampoo; soap; detergent; 2, today floor brightener; laundry wash Sushui; metal processing liquid:, spinning = agent: 93646 19 1359638 preservation of agricultural adjuvant; preservation of surfactant; preservation of diagnostic reagents; food preservation; pasteurizer for food, beverage and industrial procedures. The precise amount of the composition of the invention required to control the growth of microorganisms and higher aquatic organisms depends on the particular location to be protected. Typically, if the composition of the invention provides 0.1 to 1000 ppm isothiazole in the composition at the location a morphological component, wherein the amount of the composition is sufficient to control the growth of the microorganism at the site. The amount of the isothiazoline component of the composition present at the position is preferably at least ρ5ρρηι, at least 4 ppm is better and at least i〇 The ppm is optimal. The amount of the isothiazoline component of the composition present in this position is preferably not more than 1 〇〇〇 ppm, more preferably not more than 500 ppm, and most preferably not more than 200 ppm. In one embodiment of the invention, the composition is substantially free of an enzymatic antibiotic. Preferably, when BBIT or ΜβΙΤ is combined with methylparaben or (tetra)benzoic acid B (tetra), the composition is substantially free of an enzymatic biocide. An enzyme-based antibiotic is an enzyme having antimicrobial activity, and its meaning is, for example, a material _ special shot, please refer to 2002/0028754. ', (Example) Materials and Methods and Ratio Synergy Ratings for a Wide Range of Compound Concentrations

Eisman, pc; described in a synergistic measurement system Kull, FC; SylWestrowicz, HD and Mayer, et al., 93464 20 1359638 - < · - Microbiology 9: 538-541 (1961), an industrially accepted method, It uses the ratio determined by the following formula:

Qh/Qa + Qij/Qb = Synergy Index ("SI") where:

Qa = ppm concentration of Compound A (first component) acting alone, which produces an endpoint (MIC of Compound A).

Qa = ppm concentration of Compound A in the mixture, which produces an endpoint. QB = ppm concentration of Compound B (second component) alone. • End point (MIC of Compound B).

Qb = ppm concentration of Compound B in the mixture, which produces an endpoint. When the sum of Qa/QA and Qb/QB is greater than 丨, it indicates antagonism. When the sum of Qa/QA and Qb/QB is equal to 〖, it means that the multiplication effect' and when less than / means synergy. The lower the SI, the greater the synergy of this particular mixture. The minimum inhibitory concentration (MIC) of the antimicrobial agent is to try to detect the lowest concentration that prevents the growth of the added microorganisms under a specific set of conditions. The synergistic assay was performed using a standard microtiter assay (standard microtiter p ate assay) designed to optimize the growth of the microorganisms tested. The most salty medium (10) GY medium supplemented with 2% glucose and 〇1% yeast extract was used to test fine g; the glucose liquid medium (PDB medium) was used to test yeasts and molds. In this method, a wide range of antibacterial agents and other personal care materials are tested by high-intensity MIC analysis tests in the presence of various concentrations of strontium or barium. High resolution (iv) by adding no amount of 93646 1359638 • the same amount of antibacterial agent to one of the microtiter plates, and then performing a ten-fold serial dilution with an automated liquid handling system to obtain a series of end points of active ingredients ranging from 2 ppm to 10,000 ppm And to determine. The synergy of the combination of the invention depends on the antibacterial (E. coli (5·co//-ATCC #8739)), the yeast (Candida (C.β/Μαlike-ATCC 10231)), and the mold (black) Mildew (A «/ger-ATCC 16404)). The bacteria were used at a concentration of 5 x 106 bacteria per mL, while the yeast and mold were at 5 x 105 fungi per . These microorganisms represent natural contaminants in many consumer and industrial applications. The culture plate was visually evaluated for growth (turbidity) of the microorganisms at 25 ° C (yeast and mold) or 30 ° C (bacteria) after various culture times to determine the MIC. The results of the verification test for the synergy of the BBIT combinations of the present invention are shown in Tables 1 to 26 below. For each test, the first component (A) is BBIT and the second component (B) is another commercially available antimicrobial agent. Each table shows the specific combination of BBIT and the second component; the result of the incubation time against the detected microbial properties; the endpoint activity expressed in ppm, which is measured by BBIT alone (Qa), second The ingredients are used alone (Qb), BBIT in the mixture (Qa), and the MIC of the second component in the mixture (Qb); the calculated SI value; and each combination tested (BBIT/second The range of synergistic ratios of ingredients or A/B). The results of the verification test for the synergy of the MBIT combinations of the present invention are shown in Tables 27 to 54 below. For each test, the first component (A) is MBIT and the second component (B) is another commercially available antimicrobial agent. Each table shows the specific combination of MBIT and the second component; the result of the incubation time against the microorganisms detected in 22 93646 1359638; the endpoint activity in ppm, which is measured by MBIT alone (QA), second The ingredients are used alone (QB), MBIT in the mixture (Qa), and the MIC of the second component in the mixture (Qb); the calculated SI value; and each combination tested (MBIT/second The range of synergistic ratios of ingredients or A/B). 23 93646 1359638 Table 1 The first component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) The second component (B) = benzodiazepine chloride (Hyamine 3500)

Microorganism Qa Qb SI A/B E. coli 8139 M9GY 0 3 1.00 (48 hours) 16.667 40 1.00 1/2 10 50 1.00 1/5 12.5 60 1.00 1/5 100 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 · PDB 0 60 1.00 (24 hours) 2 4 0.40 1/2 2 5 0.42 1/3 2 6 0.43 1/3 2 8 0.47 1/4 2 10 0.50 1/5 2 20 0.67 1/10 2 30 0.83 1 /15 4 1 0.68 1/0.3 4 2 0.70 1/0.5 4 3 0.72 1/0.8 4 4 0.73 1/1 4 5 0.75 1/1 4 6 0.77 1/2 4 8 0.80 1/2 4 10 0.83 1/3 7.5 0 1.00 Microbial Qa Qb SI A/BA niger 16404 · PDB 0 200 1.00 (7 days > 5 60 0.55 1/12 5 80 0.65 1/16 5 100 0.75 1/20 10 50 0.75 1/5 10 60 0.80 1/ 6 10 80 0.90 1/8 15 4 0.77 1/0.3 15 5 0.78 1/0.3 24 93646 1359638 Microorganism Qa Qb SI A/B 15 6 0.78 1/0.4 15 8 0.79 1/0.5 15 10 0.80 1/0.7 15 20 0.85 1/1 15 30 0.90 1/2 20 0 1.00 The ratio of bismuth/chlorinated chlorinated ammonium chloride measured ranges from 1/0.02 to 1/500.

25 93646 1359638 Table 2 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = benzyl ammonium chloride Hai Yamin 1622)

Microorganism Qa Qb SI AIB Watt W8739 - M9GY 0 20 1.00 (72 hours) 40 6 0.70 1/0.2 40 8 0.80 1/0.2 40 10 0.90 1/0.3 50 3 0.65 1/0.06 50 4 0.70 1/0.08 50 5 0.75 1 /0.1 50 6 0.80 1/0.1 50 8 0.90 1/0.2 60 1 0.65 1/0.02 60 2 0.70 1/0.03 60 3 0.75 1/0.05 60 4 0.80 1/0.07 60 5 0.85 1/0.08 60 6 0.90 1/0.1 70 4 0.90 1/0.06 100 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 4 1.00 (24 hours) 4 1 0.92 1/0.3 6 0 1.00 Microbial Qa Qb SI m A. niger 16404 - PDB 0 10 1.00 (7 days) 5 4 0.65 1/0.8 5 5 0.75 1/0.8 5 6 0.85 1/1 10 4 0.90 1/0.4 20 0 1.00 The ratio of ΒΒΠ7 benzylammonium chloride is measured from 1/0.02 to 1/500. 26 93646 1359638 Table 3 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (3 ugly 11 〇 second component (B) = benzoquinone

Microorganism Qa Qb SI A/BK coJi8739 - M9GY 0 2000 1.00 (24 hours) 100 2000 0.90 1/20 200 0 1.00 — Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 3000 1.00 (48 hours) 2.5 600 0.45 1/240 2.5 800 0.52 1/320 2.5 1000 0.58 1/400 2.5 2000 0.92 1/800 5 400 0.63 1/80 5 500 0.67 1/100 5 600 0.70 1/120 5 800 0.77 1/160 5 1000 0.83 1/ 200 7.5 20 0.76 1/3 7.5 30 0.76 1/4 7.5 40 0.76 1/5 7.5 50 0.77 1/7 7.5 60 0.77 1/8 7.5 80 0.78 1/11 7.5 100 0.78 1/13 7.5 200 0.82 1/27 7.5 300 0.85 1/40 7.5 400 0.88 1/53 7.5 500 0.92 1/67 7.5 600 0.95 1/80 10 0 1.00 -... Microorganism Qa Qb SI A/B A. niger 16404 - PDB 0 5000 1.00 (3 days) 5 5000 1.13 1/1000 10 5000 1.25 1/500 15 4000 1.18 1/267 27 93646 1359638 Microbial Qa Qb SI AfB 20 5000 1.50 1/250 40 0 1.00 — The measured ratio of BBIT/phenyl sterol ranges from 1/0.2 to 1/5000. 28 93646 1359638 Table 4 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (ugly 61 butyl) Second component (B) = benzisothiazoline Ketone (BIT) Microbial Q- Qb SI ΑΓΆ E. coli 8739 - M9GY (72 hours) Microorganism C. albicans 10231 * PDB (48 hours)

& Q Microorganisms A. 72i^er 16404 - PDB (7 days)

a Q ooooooooooo 055555555 0500 0 00055 4444 5 5 5 6 602·2·7·1 1 11 1 111 81234 1 2 3 1 20 080345680 00000000800 3 1 08234568 12 1 QbQb 1.00 0.53 1/0.03 0.65 1/0.05 0.78 1/0.08 0.90 1/0.1 0.63 1/0.02 0.75 1/0.4 0.88 1/0.06 0.73 1/0.02 0.85 1/0.03 1.00 A/B 1.00 0.60 1/3. 0.67 1/4 0.77 1/0.6 0.80 1/0.8 0.83 1/1 0.87 1/1.2 0.93 1/1.6 1.00 a/R 1.00 Ά/Sj 0.86 1/16 0.33 1/2 0.43 1/3 0.53 1/4 0.63 1/5 0.73 1/6 0.93 1/8 0.27 1/0.5 0.29 1 /0.7 0.39 1/1 9 2 93646 1359638

Microorganism Qa Qb SI 15 30 0.49 1/2 15 40 0.59 1/3 15 50 0.69 1/3 15 60 0.79 1/4 20 10 0.35 1/0.5 20 20 0.45 1/1 20 30 0.55 1/2 20 40 0.65 1 /2 20 50 0.75 1/3 20 60 0.85 1/3 40 2 0.52 1/0.05 40 3 0.53 1/0.08 40 4 0.54 1/0.1 40 5 0.55 1/0.1 40 6 0.56 1/0.1 40 8 0.58 1/0.2 40 10 0.60 1/0.3 40 20 0.70 1/0,5 40 30 0.80 1/0.8 40 40 0.90 1/1 80 0 1.00 —

The ratio of ΒΒΠ7 isnzisothiazolinone measured ranges from 1/0.02 to 1/500. 30 93646 1359638 Table 5 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = 2-bromo-2-nitrate Propane-1,3-diol (BNPD) microorganism Qb si

Ε. coi?" 8739 - M9GY (48 hours) Microorganisms C. albicans 10231 - PDB (48 hours)

a Q ο ο 40404040405050505070708000

0 12 3 4 IX ο 2 444 4 4 4 44 4 44 4 466 5 1 2 3 4 1 2 1 Ο Qb 2000 1000 20 30 40 50 60 80 100 200 300 400 500 600 800 1 2 3 1.00 0.50 1/0.03 0.60 1/0.05 0.70 1/0.08 0.80 1/0.1 0.90 1/0.1 0.60 1/0.02 0.70 1/0.04 0.80 1/0.06 0.90 1/0.08 0.80 1/0.01 0.90 1/0.03 0.90 1/0.01 1.00 Am 1.00 iVJD 0.75 1/ 500 0.51 1/5 0.52 1/8 0.52 1/10 0.53 1/13 0.53 1/15 0.54 1/20 0.55 1/25 0.60 1/50 0.65 1/75 0.70 1/100 0.75 1/125 0.80 1/150 0.90 1/200 0.75 1/0.2 0.75 1/0.3 0.75 1/0.5 3 93646 1359638

Microorganism Q. Qb SI A/B 6 4 0.75 1/0.7 6 5 0.75 1/0.8 6 6 0.75 1/1 6 8 0.75 .1/1 6 10 0.76 1/2 6 20 0.76 1/3 6 30 0.77 1/ 5 6 40 0.77 1/7 6 50 0.78 1/8 6 60 0.78 1/10 6 80 0.79 1/13. 6 100 0.80 1/17 6 200 0.85 1/33 6 300 0.90 1/50 8 0 1.00 — Microbial Qa Qb SI A/B A. nlgrer 16404 - PDB 0 2000 1.00 (7 days) 5 1000 0.75 1/200 10 8 0.50 1/0.8 10 10 0.51 1/1 10 20 0.51 1/2 10 30 0.52 1/3 10 40 0.52 1/4 10 50 0.53 1/5 10 60 0.53 1/6 10 80 0.54 1/8 10 100 0.55 1/10 10 200 0.60 1/20 10 300 0.65 1/30 10 400 0.70 1/40 10 500 0.75 1 /50 10 600 0.80 1/60 10 800 0.90 1/80 20 0 1.00 — The ratio of BBIT/2-bromo-2-nitropropane-1,3-diol measured ranges from 1/0.01 to 1/500 . 32 93646 1359638 Table 6 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = butanediol

Microorganism Qa Qb SI Am E. coll 8739 - M9GY 0 20000 1.00 U8 hours) 40 5000 0.65 1/125 40 6000 0.70 1/150 40 8000 0.80 1/200 40 10000 0.90 1/250 50 2000 0.60 1/40 50 3000 0.65 1/60 50 4000 0.70 1/80 50 5000 0.75 1/100 50 6000 0.80 1/120 50 8000 0.90 1/160 70 2000 0.80 1/29 70 3000 0.85 1/43 70 4000 0.90 1/57 80 200 0.81 1/ 3 80 300 0.82 1/4 80 400 0.82 1/5 80 500 0.83 1/6 80 600 0.83 1/8 80 800 0.84 1/10 80 1000 0.85 1/13 80 2000 0.90 1/25 100 0 1.00 -... Microbial Qa Qb SI A/B C. albicans 10231 · PDB 0 20000 1.00 (24 hours) 2 10000 0.83 1/5000 4 200 0.68 1/50 4 300 0.68 1/75 4 400 0.69 1/100 4 500 0.69 1/125 4 600 0.70 1/150 4 800 0.71 1/200 4 1000 0.72 1/250 33 93646 1359638 Microorganism Qa Qb SI A/B 4 2000 0.77 1/500 4 3000 0.82 1/750 4 4000 0.87 1/1000 4 5000 0.92 1/1250 6 0 1.00 -... Microbial Qa Qb SI A/B A. 23i^er 16404 - PDB 0 10000 1.00 ...- (3 days) 5 5000 0.83 5 6000 0.93 15 0 1.00 ...- # BBIT / butylene ratio range of from 1 / 0.2 to 1/5000.

34 93646 1359638 Table 7 First component (A) = N-(n-butyl)-1,2·benzisothiazolinone (BBIT) Second component (B) = Octyl glycol microorganism Qa Qb SI A/B E. co/;8739 - M9GY 0 2000 1.00 (24 hours) 40 400 0.60 1/10 40 500 0.65 1/13 40 600 0.70 1/15 40 800 0.80 1/20 40 1000 0.90 1/25 50 200 0.60 1/4 50 600 0.80 1/12 50 800 0.90 1/16 70 200 0.80 1/3 70 300 0.85 1/4 70 400 0.90 1/6 80 200 0.90 1/3 ' 100 0 1.00 — Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 3000 1.00 (24 hours) 2 2000 0.92 1/1000 4 500 0.67 1/125 4 600 0.70 1/150 4 800 0.77 1/200 4 1000 0.83 1/250 . 6 40 0.76 1/7 6 50 0.77 1/8 6 60 0.77 1/10 6 80 0.78 1/13 6 100 0.78 1/17 6 200 0.82 1/33 6 300 0.85 1/50 6 400 0.88 1/67 6 500 0.92 1/ 83 8 0 1.00 A. niger 16404 - PDB 0 3000 1.00 35 93646 1359638 Microbial Qa Qb SI A/B (7 days) 5 1000 0.58 1/200 5 2000 0.92 1/400 10 1000 0.83 1/100 20 0 1.00 Tested The ratio of bismuth/octyl diol ranges from 1/0.2 to 1/500 0.

36 93646 1359638 Table 8 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) Second component (B) = chlorophenyl glycol ether

Microorganism Qa Qb SI A/B E. coii*8739 - M9GY 0 2000 1.00 (24 hours) 40 500 0.65 1/13 40 600 0.70 1/115 40 800 0.80 1/20 40 1000 0.90 1/25 50 300 0.65 1/ 6 50 400 0.70 1/8 50 500 0.75 1/10 50 600 0.80 1/12 50 800 0.90 1/16 70 200 0.80 1/3 70 300 0.85 1/4 70 400 0.90 1/6 80 100 0.85 1/1' 80 200 0.90 1/3 100 0 1.00 Microbial Q. Qb SI A/B C. albicans 10231 PDB 0 2000 1.00 (24 hours) 2 800 0.65 1/400 2 1000 0.75 1/500 4 300 0.65 1/75 4 400 0.70 1/100 4 500 0.75 1/125 4 600 0.80 1/150 4 800 0.90 1/200 6 10 0.76 1/2 6 20 0.76 1/3 6 30 0.77 1/5 6 40 0.77 1/7 6 50 0.78 1/ 8 6 60 0.78 1/10 6 80 0.79 1/13 6 100 0.80 1/17 37 93646 1359638 Microorganism Qa Qb SI A/B 6 200 0.85 1/33 6 300 0.90 1/50 8 0 1.00 Microbial Q» Qb SI A /B A. niger 16404 - PDB 0 2000 1.00 (4 days) 5 1000 0.83 1/200 15 0 1.00 The ratio of ΒΒΙΊ7 chlorophenylglycol measured ranges from 1/0.2 to 1/5000.

38 93646 1359638 Table 9 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (361 butyl) Second component (B) = DMDM Endogenous gland ( Hydantoin) (DMDMH) Microorganism E. coll 8739 - M9GY (72 hours)

Qb SI

.0 200 1.00 40 8 0.44 1/0.2 40 10 0.45 1/0.3 40 20 0.50 1/0.5 40 30 0.55 1/0.8 40 40 0.60 1/1 40 50 0.65 1/1 40 60 0.70 1/2 40 80 0.80 1 /2 40 100 0.90 1/3 50 3 0.52 1/0.06 50 4 0.52 1/0.08 50 5 0.53 1/0.1 50 6 0.53 1/0..1 50 8 0.54 1/0.2 50 10 0.55 1/0.2 50 20 0.60 1/0.4 50 30 0.65 1/0.6 50 40 0.70 1/0.8 50 50 0.75 . 1/1 50 60 0.80 1/1.2 50 80 0.90 1/1.6 60 6 0.63 1/0.1 60 8 0.64 1/0.1 60 10 0.65 1 /0.2 60 20 0.70 1/0.3 60 30 0.75 1/0.5 60 40 0.80 1/0.7 60 50 0,85 1/0.8 60 60 0.90 1/1 80 8 0.84 1/0.1 80 10 0.85 1/0.1 80 20 0.90 1 /0.3 39 93646 1359638 Microorganism Qa Qb SI A/B 100 0 1.00 C. albicans 10231 PDB 0 3000 1.00 (24 hours) 5 600 0.87 1/120 5 800 0.93 1/160 7.5 0 1.00 Microbial Qa Qb SI A/B A . nigerl&AQA - PDB 0 1000 1.00 (7 days) 20 80 0.33 1/4 20 100 0.35 1/5 20 200 0.45 1/10 20 300 0.55 1/15 20 400 0.65 1/20 20 500 0.75 1/25 20 600 0.85 1/30 40 100 0.60 1/3 40 200 0.70 1/5 40 300 0.80 1/8 40 400 0.90 1/ 10 80 0 1.00

The ratio of measured BBIT/DMDM intra-urea urea ranges from 1/0.2 1/5000.

40 93646 1359638

Table 10 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) Second component (B) = dithiobis(N-nonylbenzene Indoleamine) (DTBMA) Microorganism E. coJj 8139 M9GY (48 hours)

Qa Qb SI 0 60 1.00 40 6 0.50 1/0.2 40 8 0.53 1/0.2 40 10 0.57 1/0.3 40 20 0.73 1/0.5 40 30 0.90 1/0.8 50 3 0.55 1/1.06 50 4 0.57 1/0.08 50 5 0.58 1/0.1 50 6 0.60 1/0.1 50 8 0.63 1/1.2 50 10 0.67 1/0.2 50 20 0.83 1/0.4 60 3 0.65 1/0.05 60 4 0.67 1/0.07 60 5 0.68 1/008 60 6 0.70 1 /0.1 60 8 0.73 1/0.1 60 10 0.77 1/0.2 60 20 0.93 1/0.3 70 3 0.75 1/0.04 70 4 0.77 1/0.06 70 5 0.78 1/0.07 70 6 0.80 1/0.09 70 7 0.82 1/0.1 70 8 0.83 1/0.1 70 10 0.87 1/0.1 80 1 0.82 1/0.01 80 2 0.83 1/0.03 41 93646 1359638

microorganism

Qa Qb

SI

Microorganisms C. albicans 10231 ^ PDB (24 hours)

A. niger 16404 - PDB

Qa 80 3 80 4 80 5 80 6 80 8 100 0 Qb 0 2000 8 40 8 50 8 60 8 80 8 100 8 200 8 300 8 400 8 500 8 600 8 800 10 1 10 2 10 3 10 4 10 5 10 6 10 8 10 10 10 20 10 30 10 40 10 50 10 60 10 80 10 100 10 200 10 300 10 400 10 500 15 0 0 1000 0.85 1/0.04 0.87 1/0.05 0.88 1/0.06 0.90 1/0.08 0.93 1/0.1 1.00 Λ ΓΟ 1.00 ΆΠ5 0.55 1/5 0.56 1/6 0.56 1/8 0.57 1/10 0.58 1/13 0.63 1/13 0.68 1/38 0.73 1/50 0.78 1/63 0.83 1/75 0.93 · 1/100 0.67 1/0.1 0.67 1/0.2 0.67 1/0.3 0.67 1/0.4 0.67 1/0.5 0.67 1/0.6 0.67 1/0.8 0.67 1/1 0.68 1/2 0.68 1/3 0.69 .1/4 0.69 1/5 0.70 1/6 0.71 1/8 0.72 1/10 0.77 1/20 0.82 1/30 0.87 1/40 0.92 1/50 1.00 1.00 42 93646 1359638 Microorganism Qa Qb SI Am (7 days) 5 800 0.93 1/160 40 0 1.00 The ratio of BBIT/dithio-2,2'-bis(N-methylbenzamide) was measured from 1/0.02 to 1/500.

43 93646 1359638 Table 11 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (ΒΒΙΤ) Second component (Β) = ethylenediaminetetraacetic acid (EDTA) )

Microorganism Qa Qb SI A/B E. coH8139 - M9GY 0 40000 1.00 (72 hours) 40 800 0.42 1/20 40 1000 0.43 1/25 40 1200 0.43 1/30 40 1600 0.44 1/40 40 2000 0.45 1/50 40 4000 0.50 1/100 40 6000 0.55 1/150 40 8000 0.60 1/200 40 10000 0.65 1/250 40 12000 0.70 1/300 40 16000 0.80 1/400 40 20000 0.90 1/500 50 400 0.51 • 1/8 50 600 0.52 1/12 50 800 0.52 1/16 50 1000 0.53 1/20 50 1200 0.53 1/24 50 1600 0.54 1/32 50 2000 0.55 1/40 50 4000 0.60 1/80 50 6000 0.65 1/120 50 8000 0.70 1 /160 50 10000 0.75 1/200 50 12000 0.80 1/240 50 16000 0.90 1/320 60 400 0.61 1/7 60 600 0.62 1/10 60 800 0.62 1/13 60 1000 0.63 1/17 60 1200 0.63 1/20 60 1600 0.64 1/27 60 2000 0.65 1/33 44 93646

1359638 Microorganisms Microorganisms C. albicans 10231 - PDB (24 hours)

Qa Qa Qb SI A/B 60 4000 0.70 1/67 60 6000 0.75 1/100 60 8000 0.80 1/133 60 10000 0.85 1/167 60 12000 0.90 1/200 70 200 0.71 1/3 70 400 0.71 1/6 70 600 0.72 1/9 70 800 0.72 1/11 70 1000 0.73 1/14 70 1200 0.73 1/17. 70 1600 0.74 1/23 70 2000 0.75 1/29 70 4000 0.80 1/57 70 6000 0.85 1/86 70 8000 0.90 1/114 70 10000 0.95 1/143 80 400 0.81 1/5 80 600 0.82 -1/8 80 800 0.82 1/40 80 1000 0.83 1/13 80 1200 0.83 1/15 80 1600 0.84 1/20 80 2000 0.85 1/25 80 4000 0.90 1/50 80 6000 0.95 1/75 100 0 Qb 1.00 SI A/B 0 600 1.00 2.5 60 0.43 1/24 2.5 80 0.47 1/32 2.5 100 0.50 1/40 2.5 120 0.53 1/48 2.5 160 0.60 1/64 2.5 200 0.67 1/80 5 60 0.77 1/12 5 80 0.80 1/16 5 100 0.83 1/20 5 120 0.87 1/24 5 160 0.93 1/32 45 93646 1359638

Microorganism Qa Qb SI A/B 7.5 0 1.00 A. nj^er 16404 * PDB 0 1600 1.00 (7 days) 5 1000 0.75 1/200 5 1200 0.88 1/240 10 400 0.50 1/40 10 600 0.63 1/60 10 800 0.75 1/80 10 1000 0.88 1/100 15 400 0.63 1/27 15 600 0.75 1/40 15 800 0.88 1/53 20 200 0.63 1/10 20 400 0.75 1/20 20 600 0.88 1/30 40 0 1.00 The ratio of ruthenium/ethylenediaminetetraacetic acid measured ranges from 1/0.4 to 1/10000.

46 93646 1359638 Table 12 First component (A) = N-(n-butyl)-l, 2- benzoisothiazolinone (BBIT) Second component (B) = ethyl p-hydroxybenzoate Microorganism Qa Qb SI A/B E. co7i 8739 - M9GY 0 2000 1.00 (24 hours) 60 1000 0.80 1/17 80 800 0.80 1/10 80 1000 0.90 1/13 100 200 0.60 1/2 100 300 0.65 1/3 100 400 0.70 1/4 ' 100 500 0.75 1/5 100 600 0.80 1/6 100 800 0.90 1/8 200 0 1.00 Microbial Qa Qb SI A/BC, albicans 10231 PDB 0 800 1.00 (24 hours) 2.5 80 0.43 1 /32- 2.5 100 · 0.46 1/40 2.5 200 0.58 1/80 2.5 300 0.71 1/120 2.5 400 0.83 1/160 2.5 500 0.96 1/200 5 30 0.70 1/6 5 40 0.72 1/8 5 50 0.73 1 /10 5 60 0.74 1/12 5 80 0.77 1/16 5 100 0.79 1/20 5 200 0.92 1/40 7.5 0 1.00 Microbial Qa Qb SI A/B A. 16404 · PDB 0 800 1.00 (7 days) 15 600 0.94 1/40 80 0 1.00 The ratio of ΒΒΠ7-p-hydroxybenzoic acid ethyl ester measured ranges from 1/0.2 to 1/5000. 47 93646 1359638 Table 13 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = dihydroxyl ethyl sulfonate Acidate microorganism E. coli 8739 - M9GY (48 hours)

Qb SI

Microorganisms % C. albicans 10231 PDB (24 hours)

0 100 1.00 40 1 0.57 1/0.03 40 2 0.73 1/0.05 40 3 0.90 1/0.08 50 1 0.67 1/0.02 50 2 0.83 1/0.04 60 1 0.77 1/0.02 60 2 0.93 1/0.03 70 1 0.87 1/ 0.01 80 1 0.97 1/0.01 6 0 1.00 Qb SI A/B 0 10 1.00 2 4 0.60 1/2 2 5 0.70 1/2:5 2 6 0.80 1/3 4 2 0.60 1/0.5 4 3 0.70 1/0.75 4 4 0.80 1/1 4 5 0.90 1/1.3 6 1 0.70 1/0.2 6 2 0.80 1/0.3 6 3 0.90 1/0.5 8 1 0.90 1/1.1 10 0 1.00 ΒΒΙΊ7脒脒dihydroxyethyl sulfonate The ratio of acid salts ranges from 1/0.02 to 1/500. 48 93646 1359638 Table 14 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = dioctylhydropyridine

Microorganism Qa Qb SI A/B E. colj'8739 * M9GY 0 200 1.00 (72 hours) 40 10 0.33 1/0.3 40 20 0.45 1/1.5 40 30 0.58 1/0.8 40 40 0.70 1/1 40 50 0.83 1/ 1.3 40 60 0.95 1/1.5 50 10 0.38 1/0.2 50 20 0.50 1/0.4 50 30 0.63 1/0.6 50 40 0.75 1/0.8 50 50 0.88 1/1 60 4 0.35 1/0.07 60 5 0.36 1/0.08 ' 60 6 0.38 1/0.1 60 8 0.40 1/0.1 60 10 0.43 1/0.2 60 20 0.55 1/0.3 60 30 0.68 1/0.5 60 40 0.80 1/0.7 60 50 0.93 1/0.8 70 5 0.41 1/0.07 70 6 0.43 1/0.09 70 8 0.45 1/0.1 70 10 0.48 1/0.1 70 20 0.60 1/0.3 70 30 0,73 1/0.4 70 40 0.85 1/0.6 70 50 0.98 1/0.7 80 4 0.45 1/0.05 80 5 0.46 1/0.06 80 6 0.48 1/0.08 80 8 0.50 1/0.1 49 93646 1359638

microorganism

Qe

Qb

SI 3050}050,0o oo o oooooo 88 8 8 ο o oo o 000008 1 1 11 1 11111 000 0 1 2 34 5 680000 1 2 3 4 1 2 3 Microorganisms C. albicans 10231 - PDB (72 hours)

0 Q ^

SI 02 22244 446 88888880 000 1111 00 0000000000 05680000 04 5683456234 5 1 2 3 4 35801345 II , III i III i < ! ( ·5·6·7·9·5·5·5·5·5·5·6 ·6·7&0'&6:7:9:5,6'τ8,6,7,8,9,5ι5,6·6;·7;·8;·9;·6ί·6!· 7,·7: oo0·0·0·0·0·0·0·0·0·0·0·0·1·1·0·0·0·0·0·0·0·0·0 ·0·0·0·0·0·0·0·0·0·0·0·0·0·0· 8 1/0.1 1/0.3 1/0.4 1/0.51/0.011/0.02 1/0.03 1 /0.04 1/0.05 1/0.06 1/0.081/0.11/0.2 1/0.3 ooooo 1/20 1/25 1/30 1/40 1/8 1/10 1/13 1/15 1/3 1/5 1 /7 1/91/0.61/0.8 1/1 1/1 1/3 1/4 1/51/0.1 1/0.2 1/0.3 1/0.4 50 93646 1359638 Microbial Qa Qb SI. A/B 10 5 0.72 1 /0.5 10 6 0.73 1/0.6 10 8 0.75 1/0.8 10 10 0.77 1/1 10 20 0.87 1/2 10 30 0.97 1/3 15 0 1.00 Microbial Qa Qb SI A/BA niger 16404 - PDB 0 100 1.00 ( 4 days) 5 50 0.75 1/10 5 60 0.85 1/12 10 40 0.90 1/4 20 0 1.00

The ratio of BBIT/bisoctylhydropyridine tested ranged from 1/0.02 to 1/500.

51 93646 1359638 Table 15 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = hexanediol microorganism Qa Qb SI A/B E. coll 8739 - M9GY 0 20000 1.00 (24 hours) 40 20000 1.40 1/500 50 20000 1.50 1/400 60 20000 1.60 1/333 80 20000 1.80 1/250 100 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 20000 1.00 (24 hours) 2 20000 1.20 1/10000 4 20000 1.40 1/5000 6 20000 1.60 1/3333 8 20000 1.80 1/2800 10 0 1.00 Microbial Qa Qb SI A/B A. nlger 164ΌΑ * PDB 0 20000 1.00 (3 days) 5 20000 1.33 1/4000 10 20000 1.67 1/2000 15 0 1.00

The ratio of ΒΒΙΊ7 hexanediol measured ranges from 1/0.2 to 1/5000. No synergy was observed between BBIT and hexanediol. 52 93646 1359638 Table 16 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) Second component (B) = methyl p-hydroxybenzoate

Microorganism Qa Qb SI A/B E. co/i'8739 - M9GY 0 2000 1.00 (72 hours) 40 400 0.60 1/10 40 500 0.65 1/13 40 600 0.70 1/15 40 800 0.80 1/20 40 1000 0.90 1/25 50 100 0.55 1/2 50 200 0.60 1/4 50 300 0.65 1/6 50 400 0.70 1/8 50 500 0.75 1/10 50 600 0.80 1/12 50 800 0.90 1/16 60 30 0.62 1/ 0.5 · 60 40 0.62 1/0.7 60 50 0.63 1/0.8 60 60 0.63 1/1 60 80 0.64 1/1 60 100 0.65 1/2 60 200 0.70 1/3 60 300 0.75 1/5 60 400 0.80 1/7 60 500 0.85 1/8 60 600 0.90 1/10 70 300 0.85 1/4 70 400 0.90 1/6 70 500 0.95 1/7 80 300 0.95 1/4 100 0 1.00 Microbial Qa Qb SI A/B (7. albicans 10231 PDB 0 1000 1.00 (24 hours) 2.5 100 0.43 1/40 2.5 200 0.53 1/80 53 93646 1359638 Microorganism Qa Qb SI MB 2.5 300 0.63 1/120 2.5 400 0.73 1/160 2.5 500 0.83 1/200 2.5 600 0.93 1/240 5 40 0.71 1/8 5 50 0.72 1/10 5 60 0.73 1/12 5 80 0.75 1/16 5 100 0.77 1/20 5 200 0.87 1/40 5 300 0.97 1/60 * 7.5 0 1.00 Microorganisms Qa Qb SI A/B A. niger 16404 - P DB 0 1000 1.00 (3 days) 5 600 0.73 1/120 5 800 0.93 1/160 40 0 1.00

The ratio of hydrazine/p-hydroxybenzoate was measured from 1/0.2 1/5000. 54 93646 1359638 Table 17 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = pentanediol microorganism Qa Qb SI A/B E. coJj 8739 M9GY 0 20000 1.00 (24 hours) 40 20000 1.40 1/500 60 20000 1.60 1/333 80 20000 1.80 1/250 100 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 20000 1.00 (24 hours) 2 20000 1.02 1/10000 4 20000 1.04 1/5000 8 20000 1.08 10 20000 1.10 15 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 20000 1.00 (4 days) 5 20000 1.05 10 20000 1.10 15 20000 1.15 20 0 1.00

The ratio of BBIT/pentanediol measured ranges from 1/0.2 to 1/5000. No synergistic effect was observed between BBIT and pentanediol. 55 93646 1359638 Table 18 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) Second component (B) = phenoxyethanol

Microorganism Qa Qb SI A/B 尻CO" 8739 - M9GY 0 5000 1.00 (72 hours) 50 800 0.66 1/16 50 1000 0.70 1/20 50 2000 0.90 1/40 60 60 0.61 1/1 60 80 0.62 1/1 60 100 0.62 1/2 . 60 200 0.64 1/3 60 300 0.66 1/5 60 400 0.68 1/7 60 500 0.70 1/8 60 600 0.72 1/10 60 800 0.76 1/13 60 1000 0.80 1/17 70 1000 0.90 1/14 100 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 4000 1.00 (24 hours) 2.5 1000 0.58 1/400 2,5 2000 0.83 1/800 5 500 0.79 1/100 5 600 0.82 1/120 5 800 0.87 1/160 5 1000 0.92 1/200 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 4000 1.00 (7 days) 5 3000 0.88 1/600 40 0 1.00 The ratio of 7 phenoxyethanol ranges from 1/0.2 to 1/5000. 56 93646 1359638 Table 19 First component (VIII) =!^-(n-butyl)-1,2-benzisothiazolinone (361 butyl) Second component (B) = linseed oil guanamine C Propylene glycol-dianonyl ammonium phosphate (phospholipid EFA)

Microorganism Qa Qb SI Am .β W8739-M9GY 0 600 1.00 (48 hours) 40 400 0.87 1/10 50 400 0.92 1/8 200 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 * PDB 0 2000 1.00 (24 Hour) 2 800 0.60 1/400 2 1000 0.70 1/500 4 600 0.70 1/150 4 800 0.80 1/200 4 1000 0.90 1/250 6 500 0.85 1/83 6 600 0.90 1/100 10 0 1.00 Microbial Qb SI A/B A. niger 16404 - PDB 0 2000 1.00 (4 days) 5 600 0.55 1/120 5 800 0.65 1/160 5 1000 0.75 1/200 10 600 0.80 1/60 10 800 0.90 1/80 20 0 1.00 The ratio of 亚麻7 linoleum propyl propyl propylene glycol-dichloro fluorenyl phosphate was measured from 1/0.02 to 1/500. 57 93646 1359638 Table 20 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) Second component (B) = coconut oil amidinopropyl propylene glycol - gasified dimethyl ammonium phosphate (phospholipid PTC)

Microorganism Qa Qb SI E. co/z'8739 - M9GY 0 80 LOO (72 hours) 40 20 0.45 1/0.5 40 30 0.58 1/0.75 40 40 0.70 1/1 40 50 0.83 1/0.3 40 60 0.95 1/2 50 20 0.50 1/0.4 50 30 0.63 1/0.6 50 40 0.75 1/0.8 50 50 0.88 1/1 60 8 0.40 1/0.1 60 10 0.43 1/0.2 60 20 0.55 1/0.3 60 30 0.68 1/0.5 60 40 0.80 1/0.7 60 50 0.93 1/0.8 70 10 0.48 1/0.1 70 20 0.60 1/0.3 70 30 0.73 1/0.4 70 40 0.85 1/0.6 70 50 0.98 1/0.7 80 10 0.53 1/0.1 80 20 0.65 1 /0.3 80 30 0.78 1/0.4 80 40 0.90 1/0.5 100 3 0.54 1/0.3 100 4 0.55 1/0.4 100 5 0.56 1/0.5 100 6 0.58 1/0.6 100 8 0.60 1/0.8 100 10 0.63 1/0.1 58 93646 1359638 Microorganisms

Qa

Qb

SI

100 20 0.75 100 30 0.88 200 0 1.00 SI 1/0.2 1/0.3

Microorganisms A C. albicans 10231 - PDB (24 hours)

Qb 0 1000 1.00 2 600 0.73 1/300 2 800 0.93 1/400 4 400 0.67 1/400 4 500 0.77 1/125 4 600 0.87 1/150 6 300 0.70 1/50 6 400 0.80 1/67 6 500 0.90 1 /83 8 4 0.54 1/0.5 8 5 . 0.54 1/0.6 8 6 0.54 1/0.8 8 8 0.54 1/1 8 10 0.54 1/1 8 20 0.55 1/6 8 30 0.56 1/4 8 40 0.57 1/ 5 8 50 0.58 1/6 8 60 0.59 1/8 8 80 0.61 1/10 8 100 0.63 1/13 8 200 0.73 1/25 8 300 0.83 1/38 8 400 0.93 1/50 10 3 0.67 1/0.3 10 4 0.67 1/0.4 10 5 0.67 1/0.5 10 6 0.67 1/0.6 10 8 0.67 1/0.8 10 10 0.68 1/1 10 20 0.69 1/2 10 30 0.70 1/3 59 93646 1359638 Microbial Qa Qb SI A/ B 10 40 0.71 1/4 10 50 0.72 1/5 10 60 0.73 1/6 10 80 0.75 1/8 10 100 0.77 1/10 10 200 0.87 1/20 10 300 0.97 1/30 15 0 1.00 Microbial Qa Qb SI A/B A. /2J^er 16404 - PDB 0 1000 1.00 (3 days) 5 500 0.83 1/100 5 600 0.93 1/120 10 200 0.87 1/20 10 300 0.97 1/30 15 0 1.00

The ratio of BBIT/coconut oil allylpropyl propylene glycol-dianonyl ammonium phosphate was measured from 1/0.02 to 1/500.

60 93646 1359638 Table 21 First component (A) = N-(n-butyl)-1,2- benzoisothiazolinone (3 ugly 1 butyl) Second component (B) = potassium sorbate

Microorganism Qe Qb SI A/B E. 8739 - M9GY 0 20000 1.00 (24 hours) 20 20000 1.10 1/1000 40 20000 1.20 1/500 60 20000 1.30 1/333 80 20000 1.40 1/250 100 20000 1.50 1/200 200 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 400 1.00 (24 hours) 2.5 100 0.58 1/40 2.5 200 0.83 1/80 5 30 0.74 1/6 5 60 0.82 1/12 5 80 0.87 1/ 16 5 100 0.92 1/20 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 8000 1,00 (3 days) 5 6000 0.88 1/1200 10 4000 0.75 1/400 10 5000 0.88 1/500 15 4000 0.88 1/267 20 600 0.58 1/30 20 800 0.60 1/40 20 1000 0.63 1/50 20 2000 0.75 1/100 20 3000 0.88 1/150 40 0 1.00 The ratio of BBIT/potassium sorbate measured From 1/0_2 to 1/5000. 61 93646 1359638 Table 22 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = propyl paraben

Microorganism Qa Qb SI Am E. coli 8739 - M9GY 0 2000 1.00 (24 hours) 20 2000 1.10 1/100 40 2000 1.20 1/50 60 2000 1.30 1/33 80 2000 1.40 1/25 100 2000 1.50 1/25 200 0 1.00 Microbial Qa Qb SI ME C. albicans 10231e PDB 0 2000 1.00 (24 hours) 2.5 30 0.35 1/12 2.5 40 0.35 1/16 2.5 50 0.36 1/20 2.5 60 0.36 1/24 2.5 80 0.37 1/32 2.5 100 0.38 1/40 2.5 200 0.43 1/80 2.5 300 0.48 1/120 2.5 400 0.53 1/160 2.5 500 0.58 1/200 2.5 600 0.63 1/240 2.5 800 0.73 1/320 2.5 1000 0.83 1/400 5 20 0.68 1 /4 5 30 0.68 1/6 5 40 0.69 1/8 5 50 0.69 1/10 5 60 0.70 1/12 5 80 0.71 1/16 5 100 0.72 1/20 5 200 0.77 1/40 5 300 0.82 1/60 5 400 0.87 1/80 5 500 0.92 1/100 62 93646 1359638 Microorganism Qa Qb SI A/B 5 600 0.97 1/120 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 * PDB 0 2000 1.00 (7 days) ) 10 1000 0.63 1/100 20 800 0.65 1/40 20 1000 0.75 1/80 40 800 0.90 1/20 80 0 1.00 Measured ratio of ΒΒΙΊ7-p-hydroxybenzoate It ranges from 1/0.2 to _ 1/5000. 63 93646 1359638 Table 23 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = Quaternium-15 (activation-1 -(3-chloroallyl)-3,5,7-triaza-1-nitrogenadamantane chloride)

Microorganism Qa Qb SI A/B E. coli 8739 - M9GY 0 200 1.00 (72 hours) 40 50 0.43 1/1 40 60 0.43 1/1 40 80 0.44 1/2 40 100 0.45 1/3 40 200 0.50 1/5 40 300 0.55 1/8 40 400 0.60 1/10 40 500 0.65 1/13 40 600 0.70 1/15 40 800 0.80 1/20 200 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 600 1.00 ( 24 hours) 5 50 0.75 1/10 5 60 0.77 1/12 5 80 0.80 1/16 5 100 0.83 1/20 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 3000 1.00 (4 days) 10 1000 0.58 1/100 10 2000 0.92 1/200 20 1000 0.83 1/50 40 0 1.00 ΒΒΙΤ/1-(3-chloroallyl)-3,5,7-triaza-1-nitrogen The ratio of ruthenium alkane chloride ranges from 1/0.02 to 1/5000. 64 93646 1359638 Table 24 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (3 ugly 1 butyl) Second component (B) = dehydroacetic acid, sodium Salt (SDHA)

Microorganism Qa Qb SI AfB E. coJj 8739 - M9GY 0 20000 1.00 (24 hours) 20 20000 1.10 1/1000 40 20000 1.20 1/500 60 20000 1.30 1/333 80 20000 1.40 1/250 100 20000 1.50 1/200 200 0 1.00 Microorganism Qa Qb SI A/B C. albicans 10231 · PDB 0 40 1.00 (24 hours) 4 10 0.75 1/3 6 4 0.85 1/0.7 6 5 0.88 1/0.8 6 6 0.90 1/1 6 8 0.95 1/ 1 8 0 1.00 Microbial Qa Qb SI AJB A. niger 16404 - PDB 0 200 1.00 (7 days) 20 80 0.65 1/4 20 100 0.75 1/5 40 50 0.75 1/3 40 60 0.80 1/2 40 80 0.90 1 /2 80 0 1.00 The ratio of ΒΒΙΊ7 dehydroacetic acid (sodium salt) measured ranges from 1/0.02 to 1/5000. 65 93646 1359638 Table 25 First component (A) = N-(n-butyl)-l,2-benzisothiazolinone (BBIT) 第二种 Second component (Β) = sodium benzoate

Microorganism Qa Qb SI A/BR coli 8739 ' M9GY 0 20000 1.00 (24 hours) 20 20000 1.10 1/1000 40 20000 1.20 1/500 60 20000 1.30 1/333 80 20000 1.40 1/250 100 20000 1.50 1/200 200 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 2000 1.00 (48 hours) 2.5 400 0.53 1/160 2.5 500 0.58 1/200 2.5 600 0.63 1/240 2.5 800 0.73 1/320 2.5 1000 0.83 ι/ 4〇σ 5 300 0.82 1/60 5 400 0.87 1/80 5 500 0.92 1/100 5 600 0.97 1/120 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 10000 1.00 (7 days) 5 8000 0.86 1/1600 10 3000 0.43 1/300 10 4000 0.53 1/400 10 5000 0.63 1/500 10 6000 0.73 1/600 10 8000 0.93 1/800 15 3000 0.49 1/200 15 4000 0.59 1/267 15 5000 0.69 1/333 15 6000 0.79 1/400 15 7000 0.89 1/467 15 8000 0.99 1/533 66 93646 1359638

Microorganism Qa Qb SI A/B 20 1000 0.35 1/50 20 2000 0.45 1/100 20 3000 0.55 1/150 20 4000 0.65 1/200 20 5000 0.75 1/250 20 6000 0.85 1/300 20 7000 0.95 1/350 40 500 0.55 1/13 40 600 0.56 1/15 40 800 0.58 1/20 40 1000 0.60 1/25 40 2000 0.70 1/50 40 3000 0.80 1/75 40 4000 0.90 1/100 80 0 1.00 ΒΒΙΤ/Benzene measured The ratio of sodium citrate ranges from 1/0.2 to 1/5000.

67 93646 1359638 Table 26 First component (A) = N-(n-butyl)-1,2-benzisothiazolinone (BBIT) Second component (B) = sodium citrate

Microorganism Qa Qb SI A/B E. coJj 8739 - M9GY 0 20000 1.00 (24 hours) 20 20000 1.10 1/1000 40 20000 1.20 1/500 60 20000 1.30 1/333 80 20000 1.40 1/250 . 100 20000 1.50 1/ 200 200 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 10000 1.00 U8 hours) 2.5 3000 0.55 1/1200 2.5 4000 0.65 1/1600 2.5 5000 0.75 1/2000 2.5 6000 0.85 1/2400 5 600 0.56 1/120 5 800 0.58 1/160 5 1000 0.60 1/200 5 2000 0.70 1/400 5 3000 0.80 1/600 5 4000 0.90 1/800 10 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 PDB 0 10000 1.00 (3 days) 5 8000 0.93 1/1600 10 5000 0.75 1/500 10 6000 0.85 1/600 15 3000 0.68 1/200 15 4000 0.78 1/267 15 5000 0.88 1/333 15 6000 0.98 1/400 20 1000 0.60 1/50 20 2000 0.70 1/100 20 3000 0.80 1/150 68 93646 1359638 Microbial Qa Qb SI Α/Β 20 4000 0.90 1/200 40 0 1.00 The ratio of strontium/sodium citrate measured ranges from 1/0.2 to 1/5000. 69 93646 1359638 Table 27 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = N-(n-butyl) -1,2- stupid isothiazolinone (BBIT)

Microorganism Qa Qb SI A/B E. coJj'8739 - M9GY 0 100 1.00 (24 hours) 2.5 50 0.75 1/20 2.5 60 0.85 1/24 5 40 0.90 1/8 7.5 10 0.85 1/1 7.5 20 0.95 1/ 3 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 * PDB 0 6 1.00 (48 hours) 2.5 3 0.75 1/1 2.5 4 0.92 1/2 10 0 1.00 Microbial Qa Qb SI Am A. niger 16404 PDB 0 40 1.00 (4 days) 10 5 0.38 1/0.5 10 6 0.40 1/0.6 10 8 0.45 1/0.8 10 10 0.50 1/1 10 20 0.75 1/2 20 6 0.65 1/0.3 20 8 0.70 1/0.4 20 10 0.75 1/0.5 40 0 1.00 The measured ratio of MBIT/BBIT ranges from 1/0.01 to 1/400. 70 93646 1359638 Table 28 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = gasified benzodiazepine ( Hyamine 3500) Microbial SI A/B-- B. coL 8739-M9GY (24 hours) ο 2 5 5 0 7-L0 Microorganism C. albicans 10231 * PDB (24 hours)

a Q Microorganism A. niger 16404 PDB (4 days)

a Q 0222244444446666668 ο ο ο ο ο ο ο 111111

Qb Qb 10 1.00 4 1.25 1/2 3 1.25 1/0.6 3 1.50 1/0.4 0 1.00 SI A/B 60 1.00 10 0.42 1/5 20 0.58 1/10 30 0.75 1/15 40 0.92 1/20 3 0.55 1 /0.8 4 0.57 1/1 5 0.58 1/1 6 0.60 1/2 8 0.63 1/2 10 0.67 1/3 20 0.83 1/5 3 0.80 1/0.5 4 0.82 1/0.7 5 0.83 1/0.9 6 0.85 1 /1 8 0.88 1/1 10 0.92 1/2 0 1.00 SI A/B 200 1.00 30 0.48 1/3 40 0.53 1/4 50 0.58 1/5 60 0.63 1/6 80 0.73 1/8 100 0.83 1/10 93646 1359638 Microorganism Qa Qh SI A/B 20 4 0.69 1/0.2 20 5 0.69 1/0.3 20 6 0.70 1/0.3 20 8 0.71 1/0.4 20 10 0.72 1/0.5 20 20 0.77 1/4 20 30 0.82 1/ 1.5 20 40 0.87 1/2 20 50 0.92 1/3 20 60 0.97 1/3 30 0 1.00 The ratio of MBIT/gasified stearidine ammonium is measured from 1/0.01 to 1/400.

72 93646 1359638 Table 29 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = Ammonium chloride chlorinated (sea) Yamin 1622) Microorganism Qa Qb SI A/B E. coli 8739 - M9GY 0 20 1.00 (24 hours) 2.5 20 1.25 1/8 5 20 1.50 1/4 7.5 5 1.00 1/0.7 10 0 1.00 Microbial Qa Qb SI A /B C. albicans 10231 * PDB 0 4 1.00 (hours) 2 3 1.00 1/2 4 3 1.25 1/0.8 6 1 1.00 1/0.2 8 0 1.00 Microbial Qa 0>. SI A/B A. niger 16404 - PDB 0 10 1.00 (4 days) 10 4 0.73 1/0.4 10 5 0.83 1/0.5 10 6 0.93 1/0.6 30 0 1.00

The ratio of MBIT/ammonium chloride chlorinated was measured from 1/0.01 to 1/400. 73 93646 1359638 Table 30 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = benzoquinone

Microorganism Qa Qb SI A/B 亘W8739 _ M9GY 0 5000 1.00 (24 hours) 2.5 5000 1.25 1/2000 5 4000 1.30 1/800 7.5 4000 1.55 1/533 10 0 1.00 — Microorganisms ' Qa Qb SI A/B C. Albicans 10231 · PDB 0 4000 1.00 (48 hours) 2.5 2000 0.75 1/800 5 500 0.63 1/100 5 1000 0.75 1/200 7.5 40 0.76 1/5 7.5 50 0.76 1/7 7.5 60 0.77 1/8 7.5 80 0.77 1/11 7.5 100 0.78 1/13 7.5 200 0.80 1/27 7.5 300 0.08 1/40 7.5 400 0.85 1/53 7.5 500 0.88 1/67 7.5 600 0.90 1/80 ' 7.5 800 0.95 1/107 10 0 1.00 Microorganisms Qa Qb SI A/BA niger 16404 PDB 0 6000 1.00 (4 days) 10 6000 1.20 1/600 20 6000 1.40 1/300 30 4000 1.27 1/133 50 0 1.00 — The measured ratio of MBIT/phenyl sterol ranges from 1/0.1 to 1/4000. 74 93646 1359638 Table 31 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = Benzoisothiazolinone (BIT )

Microbial Ο» Qb SI A/B E. coli 8739 - M9GY 0 20 1.00 (24 hours) 2.5 10 0.75 1/4 5 5 0.75 1/1 . 5 6 0.80 1/1 5 8 0.90 1/2 7.5 3 0.90 1 /0.4 7.5 4 0.95 1/0.5 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 30 1.00 (48 hours) 2.5 10 0.58 1/4 2.5 20 0.92 1/8 5 4 0.63 1/0.8 5 5 0.67 1/1 5 6 0.70 1/1 5 8 0.77 1/2 5 10 0.83 1/2 7.5 2 0.82 1/0.3 7.5 3 0.85 1/0.4 7.5 4 0.88 1/0.5 7.5 5 0.92 1/0.7 7.5 6 0.95 1 /0.8 10 0 1.00 Microbial Qa Qb SI A/BA, niger 16404 PDB 0 300 1.00 (7 days > 10 100 0.53 1/10 10 200 0.87 1/20 20 30 0.50 1/2 20 40 0.53 1/2 20 50 0.57 1/3 20 60 0.60 1/3 20 80 0.67 1/4 20 100 0.73 1/5 J 75 93646 1359638 Microorganism Qa Qb SI Am 30 20 0.67 1/0.7 30 30 0.70 1/1 30 40 0.73 1/1 30 50 0.77 1/2 30 60 0.80 1/2 30 80 0.87 1/3 30 100 0.93 1/3 50 0 1.00 The ratio of MBIT/benzisothiazolinone measured ranges from 1/0.01 to 1/400.

76 93646 1359638 Table 32 First component (A) = Ν· decyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = 2-bromo-2-nitro Propane-1,3-diol) (BNPD)

Microorganism Qa Qb SI

E. coZ? 8739 - M9GY (24 hours) Microorganisms C. albicans 10231 PDB (24 hours)

a Q 05555 5 5 ο 2.7·7·1 0 4 4 4 4 6 6666666666668 Microorganisms A. niger 16404 - PDB (4 days)

0 Q ο ο ο ο 112

Qb Qb 8 1.00 5 0.88 1/2 1 0.63 1/0.2 2 0.75 1/0.4 3 0.88 1/0.6 1 0.88 1/0.1 2 1.00 1/0.3 0 1.00 t) SI A/B 1000 1.00 100 0.60 1/25 200 0.70 1/50 300 0.80 1/75 400 0.90 1/100 4 0.75 1/0.7 5 0.76 1/0.8 6 0.76 1/1 8 0.76 1/1 10 0.76 1/2 20 0.77 1/3 30 0.78 1/5 40 0.79 1/7 50 0.80 1/8 60 0.81 1/10 80 0.83 1/13 100 0.85 1/17 200 0.95 1/33 0 1.00 » SI A/B 2000 1.00 800 0.60 0/80 1000 0.70 1/100 5 0.40 1/0.3 77 93646 1359638 Microorganism Qa Qb SI A/B 20 6 0.40 1/0.3 20 8 0:40 1/0.4 20 10 0.41 1/0.5 20 20 0.41 1/1 20 30 0.42 1/2 20 40 0.42 1/ 2 20 50 0.43 1/3 20 60 0.43 1/3 20 80 0.44 1/4 20 100 0.45 1/5 20 200 0.50 1/10 20 300 0.55 1/15 _ 20 400 0.60 1/20 20 500 0.65 1/25 20 600 0.70 1/30 20 800 0.80 1/40 20 1000 0.90 1/50 30 0 1.00

The ratio of MBIT/2-bromo-2-nitropropane-1,3-diol measured ranged from 1/0.01 to 1/400.

78 93646 1359638 Table 33 First component (A) = N-mercapto-1,2·benzisothiazolin-3-one (MBIT) Second component (B) = butanediol

Microorganism Qa Qb SI A/B E. coi/ 8739 - M9GY 0 20000 1.00 (24 hours) 2.5 20000 1.33 1/8000 5 20000 1.67 1/4000 7.5 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 20000 1.00 (72 hours) 8 100 0.81 1/13 8 200 0.81 1/25 8 300 0.82 1/38 8 400 0.82 1/50 8 500 0.83 1/63 8 600 0.83 1/75 8 800 0.84 1/100 8 1000 0.85 1/125 8 2000 0.90 1/250 8 3000 0.95 1/375 10 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 * PDB 0 10000 1.00 — (7 days) 10 10000 1.25 1/1000 20 10000 1.50 1/ 500 30 10000 1.75 1/333 40 0 1.00 — The ratio of MBIT/butanediol measured ranges from 1/0.1 to 1/4000. 79 93646 1359638 Table 34 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT)

The second component (B) = octopine di-alcohol microorganism Qa Qb SI A/BK coJJ 8739 M9GY 0 2000 1.00 (24 hours) 2.5 2000 1.25 1/800 5 2000 1.50 1/400 7.5 2000 1.75 1/267 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 4000 1.00 (24 hours) 2 2000 0.70 1/1000 2 3000 0.95 1/1500 4 2000 0.90 1/500 6 600 0.75 1/100 6 800 0.80 1/ 133 6 1000 0.85 1/167 8 200 0.85 1/25 8 300 0.88 1/38 8 400 0.90 1/50 8 500 0.93 1/63 8 600 0.95 1/75 10 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 1000 1.00 (4 days) 10 1000 0.58 1/100 10 2000 0.83 1/200 20 1000 0.92 1/50 20 0 1.00 The ratio of MBIT/octyl diol measured ranges from 1/0.1 to 1/ 4000. 80 93646 1359638 Table 35 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = chlorophenyl glycol ether

Microorganism Qa Qb SI A/B E. co7i8739*M9GY 0 2000 1.00 (24 hours) 7.5 800 0.90 1/107 15 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 2000 1.00 (72 hours) 4 200 0.50 1/50 4 300 '0.55 1/75 4 400 0.60 1/100 4 500 0.65 1/125 4 600 0.70 1/150 4 800 0.80 1/200 4 1000 0.90 1/250 6 80 0.64 1/13 6 100 0.65 1/17· 6 200 0.70 1/33 6 300 0.75 1/50 6 400 0.80 1/67 6 500 0.85 1/83 6 600 0.90 1/100 8 40 0.82 1/5 8 50 0.83 1/6 8 60 0.83 1 /8 8 80 0.84 1/10 8 100 0.85 1/13 8 200 0.90 1/25 8 300 0.95 1/38 10 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 PDB 0 2000 1.00 (3 days) 10 2000 1.50 1/200 20 0 1.00 The ratio of MBIT/chlorophenylglycol measured ranges from 1〇_1 to 1/4000. 81 93646 1359638 Table 36 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = DMDM Hydantoin (DMDMH) Microbial Qa Qb SI A/B E. coJj 8139 - M9GY 0 50 1.00 (24 hours) 2.5 60 1.45 1/24 5 30 1.10 1/6 7.5 10 0.95 1/1 10 0 1.00 ..... * Microorganism Qa Qb SI A/B C. albicans 10231 PDB 0 3000 1.00 (24 hours) 2.5 3000 1.33 1/1200 5 1000 1.00 1/200 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 · PDB 0 1000 1.00 (3 days) 10 2000 2.25 1/200 20 2000 2.50 1/100 40 0 1.00

The ratio of MBIT/DMDM in the measured MBI/DMDM ranged from 1/0.1 to 1/4000. No synergistic effect was observed between MBIT and DMDM. 82 93646 1359638

Table 37 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = dithio-2,2'-double ( N-methylbenzamine) (DTBMA) Microbial Qa Qb SI A/B E. c〇7/8739 - M9GY 0 80 1.00 (24 hours) 2.5 20 0.42 1/8 2.5 30 0.54 1/12 2.5 40 0.67 1/16 2.5 50 0.79 1/20 2.5 60 0.92 1/24 5 20 0.58 1/4 5 30 0.71 1/6 5 40 0.83 1/8 5 50 0.96 1/10 7.5 3 0.54 1/0.4 7.5 4 0.55 1/ 0.5 7.5 5 0.56 1/0.7 7.5 6 0.58 1/0.8 7.5 8 0.60 1/1 7.5 10 0.63 1/1 7.5 20 0.75 1/3 7.5 30 0.88 1/4 10 1 0.68 1/0.1 10 2 0.69 1/0.2 10 3 0.70 1/0.3 10 4 0.72 1/0.4 10 5 0.73 1/0.5 10 6 0.74 1/0.6 10 8 0.77 1/0.8 10 10 0.79 1/1 10 20 0.92 1/2 15 0 1.00 Microbial Qa SI A/B C. albicans 10231 PDB 0 2000 1.00 (24 hours) 6 60 0.63 1/10 6 80 0.64 1/13 83 93646 1359638 Microorganism Qa Qb SI A/B 6 100 0.65 1/17 6 200 0.70 1/33 6 300 0.75 1 /50 6 400 0.80 1/67 6 500 0.85 1/83 6 600 0.90 1/100 8 10 0.81 1/1 8 20 0.81 1/3 8 30 0.8 2 1/4 8 40 0.82 1/5 8 50 0.83 1/6 8 60 0.83 1/8 8 80 0.84 1/10 8 100 0.85 1/13 8 200 0.90 1/25 8 300 0.95 1/38 10 0 1.00 Microorganisms Qa Qb SI A/B A. niger 16404 - PDB 0 800 1.00 (3 days) 10 500 0.96 1/50 30 0 1.00

The ratio of MBIT/dithio-2,2'-bis(N-mercaptobenzamide) was measured from 1/0.01 to 1/400. 84 93646 1359638 Table 3 8 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = ethylenediaminetetraacetic acid (EDTA) Microbial Qe Qt> SI A/B E. c〇yy 8739 - M9GY 0 40000 1.00 (24 hours) 5 1600 0.54 1/320 10 0 1.00 Microbial Qa Qb SI A/BC: albicans 10231 · PDB 0 1000 1.00 (48 Hour) 2.5 60 0.43 1/24 2.5 80 0.47 1/32 2.5 100 0.50 1/40 2.5 120 0.53 1/48 7.5 0 1.00 Microbial Qa Qb SI A/BA 16404 - PDB 0 1600 1.00 (3 days) 10 800 0.75 1 /80 10 1000 0.88 1/100 20 200 0.63 1/10 20 400 0.75 1/20 20 600 0.88 1/30 40 0 1.00

The ratio of MBIT/ethylenediaminetetraacetic acid measured ranges from 1/0.3 to 1/8000. 85 93646 1359638 Table 39 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = p-hydroxybenzoic acid ethyl ester microorganism Qa Qb SI A/B and W8739 · M9GY 0 2000 1.00 (24 hours) 2.5 2000 1.25 1/800 5 2000 1.50 1/400 7.5 400 0.95 1/53 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 * PDB 0 2000 1.00 (24 hours) 2.5 600 0.63 1/240 2.5 800 0.73 1/320 2.5 1000 0.83 1/400 2.5 2000 1.33 1/800 5 50 0.69 1/10 5 60 0.70 1/12 5 80 0.71 1/16 5 100 0.72 1/20 5 200 0.77 1/40 5 300 0.82 1/60 5 400 0.87 1/80 5 500 0.92 1/100 5 600 0.97 1/120 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 · PDB 0 800 1.00 (7 days) 30 200 0.85 1/7 30 300 0.98 1/10 50 0 1.00

The ratio of MBIT/p-hydroxybenzoate ethyl ester measured ranges from 1/0.1 to 1/4000 ° 86 93646 1359638 Table 40 First component (A) = N-methyl-1,2-benzisothiazole Porphyrin-3-one (MBIT) Second component (B) = hexamethylene dihydroxyethyl sulfonate microorganism Qa Qb SI A/B E. coli81Sd - M9GY 0 8 1.00 (24 hours) 2.5 8 1.17 1/3 5 8 1.33 1/2 7.5 5 1.13 1/0.7 10 3 1.04 1/0.3 15 0 1.00 Microbial Qa Qb SI A/BC albicans 10231 - PDB 0 10 1.00 (24 hours) 2 5 0.70 1/3 2 6 0.80 1/ 3 4 4 0.80 1/1 4 5 0.90 1/1 8 1 0.90 1/0.1 10 0 1.00

The ratio of MBIT/hexamethylene disulfonate measured ranges from 1/0.01 to 1/400.

87 93646 1359638

Table 41 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = dioctylhydrogenidine microorganism Qa Qb SI A/B E. coHS139 - M9GY 0 80 1.00 (72 hours) 5 40 0.83 1/8 5 50 0.96 1/10 15 0 1.00 Microbial Qa Qb SI A/B 'albicans 10231 - PDB 0 80 1.00 (72 hours) 2 40 0.53 1 /20 2 50 0.63 1/25 2 60 0.73 1/30 2 80 0.93 1/40 4 30 0.57 1/8 4 40 0.67 1/10 4 50 0.77 1/13 4 60 0.87 1/15 6 20 0.60 1/3 6 30 0.70 1/5 6 40 0,80 1/7 6 50 0.90 1/8 8 5 0.58 1/0.6 8 6 0.59 1/0.7 8 8 0.61 1/1 8 10 0.63 1/1 8 20 0.73 1/3 8 30 0.83 1/4 8 40 0.93 1/5 10 1 0.68 1/0.1 10 2 0.69 1/0.2 10 3 0.70 1/0.3 15 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 * PDB 0 200 1. Q0 (3 days) 10 40 0.53 1/4 10 50 0.58 1/5 88 93646 1359638 Microorganism Qa Qb SI A/B 10 60 0.63 1/6 10 80 0.73 1/8 10 100 0.83 1/10 20 20 0.77 1/ 1 20 30 0.82 1/2 20 40 0.87 1/2 20 50 0.92 1/3 20 60 0.97 1/3 20 0 1.00 The ratio of MBIT/bisoctylhydropyridine measured ranges from 1/0.01 to 1/400.

89 93646 1359638 Table 42 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = hexanediol microorganism Qa Qb SI AfB E. coJi 8139 - M9GY 0 20000 1.00 (24 hours) 2.5 20000 1.17 1/8000 5 20000 1.33 1/4000 7.5 20000 1.50 1/2667 10 20000 1.67 1/2000 15 0 1.00 Microbial Qb Qb SI A/B C. albicans 10231 - PDB 0 20000 1.00 (24 hours) 2 20000 1.13 1/10000 4 20000 1.27 1/5000 6 20000 1.40 1/3333 8 20000 1.53 1/2500 10 20000 1.67 1/2000 15 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 20000 1.00 (3 days) 10 20000 1.33 1/2000 20 20000 1.67 1/1000 30 0 1.00

The ratio of MBIT/hexanediol measured ranges from 1/0.1 to 1/10000. No synergistic effect was observed between MBIT and hexanediol. ‘ 90 93646 1359638 Table 43 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = oxime hydroxybenzoate

Microorganism Qa Qb SI A/B E. coJi 8739 - M9GY 0 2000 1.00 (24 hours) 2.5 2000 1.25 1/800 5 2000 1.50 1/400 7.5 800 1.15 1/107 10 0 1.00 Microbial Qa Qb SI A/B C. Albicans 10231 - PDB 0 2000 1.00 (48 hours) 2.5 1000 0.83 1/400 5 400 0.87 1/80 5 500 0.92 1/100 5 600 0.97 1/120 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 · PDB 0 800 1.00 (7 days) 30 50 0.66 1/2 30 60 0.68 1/2 30 80 0.70 1/3 30 100 0.73 1/6 30 200 0.85 1/7 30 300 0.98 1/10 50 0 1.00 The ratio of MBIT/glycol hydroxybenzoate ranges from 1/0.1 to 1/4000. 91 93646 < s 1359638 Table 44 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = pentanediol microorganism Q Qb SI A/B E. coil 8739 - M9GY 0 20000 1.00 (24 hours) 2.5 20000 1.17 1/8000 5 20000 1.33 1/4000 7.5 20000 1.50 1/2667 10 20000 1.67 1/2000 15 0 1.00 Microbial Qe Qb SI A/B C. albicans 10231 - PDB 0 20000 1.00 (24 hours) 2 20000 1.13 1/10000 4 20000 1.27 1/5000 8 20000 1.53 1/2500 10 0 1.00 Microbial Qa Qb SI A/BA 722^^16404 * PDB 0 20000 1.00 (3 days) 10 20000 1.67 1/2000 20 20000 2.33 1/1000 30 0 1.00

The ratio of MBIT/pentanediol measured ranged from 1/0.1 to 1/10000 ° 无 and no synergistic effect was observed between pentanediol. 92 93646 1359638 Table 45 First component (A) = N-fluorenyl 1,2-benzisothiazolin-3-one (MBIT) Second component (B) = phenoxyethanol microorganism Qa Qb SI A/BR coJJ 8139 - M9GY 0 4000 1.00 (24 hours) 2.5 4000 1.17 1/1600 5 4000 1.33 1/800 7.5 4000 1.50 1/533 10 3000 1.42 1/300 40 3000 3.42 1/75 15 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 3000 1.00 (24 hours) 5 600 0.87 1/120 5 800 0.93 1/160 7.5 0 1.00 Microbial Qa Qb SI A/BA niger 16404 * PDB 0 4000 1.00 (3 days) 10 4000 1.25 1/400 20 2000 1.00 1/100 40 0 1.00

The ratio of MBIT/phenoxyethanol measured ranges from 1/0.1 to 1/4000. 93 93646 1359638 Table 46 First component (A) = N-methyl·1,2-benzisothiazolin-3-one (MBIT) Second component (B) = linseed oil allylpropyl propylene glycol - Dimethylammonium chloride phosphate (filler EFA)

Microorganism Qa Qb SI A/B E. coi?'8739 - M9GY 0 500 1.00 (48 hours) 15 40 0.83 1/3 15 50 0.85 1/3 15 60 0.87 1/4 15 80 0.91 1/5 15 100 0.95 1 /7 20 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 1000 1.00 (24 hours) 2 800 0.93 1/400 4 600 0.87 1/150 6 500 0.90 1/83 15 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 PDB 0 2000 1.00 (3 days) 10 800 0.73 1/80 10 1000 0.83 1/100 20 300 0.82 1/15 20 400 0.87 1/20 20 500 0.92 1/25 20 600 0.97 1/ 30 30 0 1.00 The ratio of MBIT/linsein guanidinium propyl propylene glycol-dianonyl ammonium phosphate was measured from 1/0.01 to 1/400. 94 93646 1359638 Table 47 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = coconut oil allylpropyl propylene glycol - Dimethylammonium chloride phosphate (phospholipid PTC)

Microorganism Qa Qb SI A/B Ε. οού 8139 - M9GY 0 100 1.00 (48 hours) 2.5 60 0.73 1/24 2.5 80 0.93 1/32 10 30 0.80 1/3 10 40 0.90 1/4 15 10 0.85 1/0.7 15 20 0.95 1/1 20 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 · PDB 0 1000 1.00 (24 hours) 4 500 0.90 1/125 6 300 0.90 1/50 8 3 0.80 1/0.4 8 4 0.80 1/0.5 8 5 0.81 1/0.7· 8 6 0.81 1/0.8 8 8 0.81 1/1 8 10 0.81 1/1 8 20 0.82 1/3 8 30 0.83 1/4 8 40 0.84 1/5 8 50 0.85 1 /6 8 60 0.86 1/8 8 80 0.88 1/10 8 100 0.90 1/13 10 0 1.00 Microbial Qa Qb SI Am A 16404 - PDB 0 1000 1.00 (4 days) 10 500 0.83 1/50 10 600 0.93 1/ 60 30 0 1.00 The measured ratio of MBIT/coconut oil guanidinium propyl propylene glycol to diammonium chlorophosphate is from 1/0.01 to 1/400. 95 93646 1359638

Table 48 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = potassium sorbate microorganism Qa Qb SI Am E. coJi 8139 M9GY 0 20000 1.00 (48 hours) 10 1000 0.72 1/100 10 2000 0.77 1/200 10 3000 0.82 1/300 10 4000 0.87 1/400 10 5000 0.92 1/500 10 6000 0.97 1/600 15 0 1.00 Microbial Qa Qb SI Am C. albicans 10231 PDB 0 400 1.00 (24 hours) 2.5 200 0.83 1/80 5 40 0.77 1/8 5 50 0.79 1/10 5 60 0.82 1/12 5 80 0.87 1/16 5 100 0.92 1/ 20 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 10000 1.00 (4 days) 10 6000 0.85 1/600 20 1000 0.60 1/50 20 2000 0.70 1/100 20 3000 0.80 1/150 20 4000 0.90 1/200 40 0 1.00 The ratio of MBIT/potassium sorbate measured ranges from 1/0.1 to 1/4000. 96 93646 1359638 Table 49 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = propyl paraben

Microorganism Qe Qb SI Am E. coh 8139 * M9GY 0 4000 1.00 (48 hours) 2.5 2000 0.67 1/800 2.5 3000 0.92 1/1200 5 2000 0.83 1/400 15 0 1.00 Microbial Q- Qb SI A/B C. albicans 10231 · PDB 0 2000 1.00 (24 hours) 2.5 800 0.73 1/320 2.5 1000 0.83 1/400 5 400 0.87 1/80 5 500 0.92 1/100 5 600 0.97 1/120 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 2000 1.00 (7 days) 10 800 0.60 1/80 10 1000 0.70 1/100 20 1000 0.90 1/50 30 300 0.75 1/10 30 400 0.80 1/13 30 500 0.85 1/17 30 600 0.90 1/20 50 0 1.00 The ratio of MBIT/propylparaben measured ranges from 1/0.1 to 1/4000 ° 97 93646 1359638 Table 50 First component (A) = N-fluorenyl- 1,2-Benzoisothiazolin-3-one (MBIT) Second component (B) = Quaternium-15 (activated-1-(3-chloroallyl)-3,5,7-triaza -1-Aza-adamantane chloride) Microbial Qa Qb SI A/B E. coJi 8739 - M9GY 0 50 1.00 (24 hours) 5 20 0.90 1/400 7.5 2 0.79 1/0.3 7.5 3 0.81 1/0.4 7.5 4 0.83 1/0.5 7.5 5 0.85 1/0.7 7.5 6 0.87 1/0.8 7.5 8 0.91 1/1 7.5 10 0.95 1/1 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 PDB 0 500 1.00 (24 hours) 2.5 500 1.33 1/200 5 300 1.27 1/60 7.5 0 1.00 Microorganisms Qa Qb SI A/B A. niger 16404 - PDB 0 3000 1.00 (3 days) 10 1000 0.58 1/100 10 2000 0.92 1/200 20 1000 0.83 1/50 40 0 1.00

The ratio of ruthenium / 1-(3-chloroallyl)-3,5,7-triaza-1-azaindene adamantane chloride was measured from 1/0.01 to 1/4000. 98 93646 1359638 Table 51 First component (A) = N-methyl-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = dehydroacetic acid, sodium salt (SDHA) Microorganism Qa Qb SI A/B E. co/i'8739 * M9GY 0 20000 1.00 (24 hours) 2.5 20000 1.25 1/8000 5 20000 1.50 1/4000 7.5 20000 1.75 1/2667 10 0 1.00 Microbial Qb Qb SI A /B C. albicans 10231 - PDB 0 40 1.00 (24 hours) 2 40 1.25 1/20 4 30 1.25 1/8 6 8 0.95 1/1 8 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 PDB 0 200 1.00 (7 days) 20 80 0.80 1/4 20 100 0.90 1/5 30 50 0.85 1/2 30 60 0.90 1/2 50 0 1.00

The ratio of MBIT/dehydroacetic acid (sodium salt) measured ranges from 1/0.01 to 1/4000 ° 99 93646 1359638

Table 52 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = sodium benzoate microorganism Qa Q» SI A/ B E. coi/'8739-M9GY 0 10000 1.00 (24 hours) 2.5 10000 1.25 1/4000 5 10000 1.50 1/2000 7.5 10000 1.75 1/1333 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231e PDB 0 2000 1.00 (48 hours) 2.5 800 0.65 1/320 2.5 1000 · 0.75 1/400 5 300 0.65 1/60 5 400 0.70 1/80 5 500 0.75 1/100 5 600 0.80 1/120 5 800 0.90 1/160 7.5 30 0.77 1/4 7.5 40 0.77 1/5 7.5 50 0.78 1/7 7.5 60 0.78 1/8 7.5 80 0.79 1/11 7.5 100 0.80 1/13 7.5 200 0.85 1/27 7.5 300 0.90 1/40 7.5 400 0.95 1/53 10 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 10000 1.00 (7 days) 10 6000 0.77 1/600 10 8000 0.97 1/800 20 6000 0.93 1/300 30 2000 0.70 1/67 30 3000 0.80 1/100 30 4000 0.90 1/133 40 2000 0.87 1/50 100 93646 1359638 Microbial Qa Qb SI A/B 40 3000 0.97 1/75 60 0 1.00 The ratio of MBIT/sodium benzoate measured ranges from 1/0.1 to 1/40 00. 101 93646 1359638 Table 53 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = sodium citrate

Microorganism Qa Qb SI A/B E. c^8739 - M9GY . 0 20000 1.00 (24 hours) 2.5 20000 1.25 1/8000 5 20000 1.50 1/4000 7.5 20000 1.75 1/2667 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 * PDB 0 10000 1.00 (24 hours) 2.5 3000 0.63 1/1200 2.5 4000 0.73 1/1600 2.5 5000 0.83 1/2000 2.5 6000 0.93 1/2400 5 500 0.72 1/100 5 600 0.73 1/120 5 800 0.75 1/160 5 1000 0.77 1/200 5 2000 0.87 1/400 5 3000 0.97 1/600 7.5 0 1.00 Microbial Qa Qb SI A/B A. niger 16404 - PDB 0 10000 1.00 (7 days) 30 1000 0.70 1 /33 30 2000 0.80 1/67 30 3000 0.90 1/100 50 0 1.00 The ratio of MBIT/sodium citrate measured ranges from 1/0.1 to 1/4000. 102 93646 1359638

Table 54 First component (A) = N-mercapto-1,2-benzisothiazolin-3-one (MBIT) Second component (B) = ° ratio of zinc chelate zinc microbe Qa Qb SI A /B E. coJi 8739 - M9GY 0 2 1.00 (48 hours) 2.5 0.4 0.45 1/0.2 2.5 0.5 0.50 1/0.2 2.5 0.6 0.55 1/0.2 2.5 0.8 0.65 1/0.3 2.5 1 0.75 1/0.4 5 0.3 0.65 1/ 0.06 5 0.4 0.70 1/0.08 5 0.5 0.75 1/0.1 5 0.6 0.80 1/0.1 5 0.8 0.90 1/0.2 7.5 0.3 0.90 1/0.04 7.5 0.4 0.95 1/0.05 10 0 1.00 Microbial Qa Qb SI A/B C. albicans 10231 - PDB 0 30 1.00 (72 hours) 2.5 4 0.47 1/2 2.5 5 0.50 1/2 2.5 6 0.53 1/2 2.5 8 0.60 1/3 2.5 10 0.67 1/4 5 2 0.73 1/0.4 5 3 0.77 1 /0.6 5 4 0.80 1/0.8 5 5 0.83 1/1 5 6 0.87 1/1 5 8 0.93 1/2 7.5 0 1.00 A. niger 16404 * PDB 0 20 1.00 (3 days) 20 5 0.75 1/3 20 6 0.80 1/0.3 20 8 0.90 1/0.4 40 0 1.00 The ratio of measured MBIT/zinc pyrithione zinc ranges from 1/0.001 to 1/400. 103 93646

Claims (1)

An antibacterial composition comprising: (a) N-(n-butyl)-1,2-benzisoindole _3_ ah, and (b) benzyl alcohol, 八中(正· Butyl)-〗, the weight ratio of 2-benzisoindolone to benzyl alcohol is 1:1 to 1 ··1000. 2. The antibacterial composition of the invention of claim </ RTI> wherein the weight ratio of n_(n-butyl)-1,2-benzisothiazolin-3-enone to benzyl alcohol is 1:2 to 1: 800 ° 3. The antibacterial composition of claim 2, wherein the weight ratio of N_(n-butyl)-1,2-benzisothiazoline-3-one to benzyl alcohol is from u to 1: 800 ° 4. An antibacterial composition comprising: (a) N-mercapto-i, 2-benziso D-Serazine -3- ketone; and (b) phenyl sterol, - The weight ratio of N-methyl-l,2_benzisoindole 0 sitin-3__ to stupid methanol is 1:1 to 1:8 〇〇. 5. The antibacterial composition of claim 4, wherein the weight ratio of n-methyl-1,2-exidoisothiazoline_3__ to claudyl alcohol is 1 1·ROO 〇93646 revision 104